Datasets:

linjc16
/

ctgov

nct_id stringlengths 11 11	brief_title stringlengths 7 300	brief_summary stringlengths 0 4.99k	detailed_descriptions stringlengths 0 31.8k	official_title stringlengths 16 598 ⌀	conditions stringlengths 0 11k	interventions stringlengths 0 3.18k	eligibility_criteria stringlengths 0 19.6k ⌀	minimum_age stringclasses 304 values	maximum_age stringclasses 448 values	gender stringclasses 4 values	healthy_volunteers stringclasses 3 values	design_details stringlengths 0 1.17k	primary_outcome_measures stringlengths 75 136k	secondary_outcome_measures stringlengths 0 185k	keywords stringlengths 0 18.8k	mesh_terms stringlengths 0 8.39k	arms_and_interventions stringlengths 0 109k	structured_text stringlengths 539 193k
NCT00170157	Hormone Therapy and Ipilimumab in Treating Patients With Advanced Prostate Cancer	RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin, flutamide, or bicalutamide may lessen the amount of androgens made by the body. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving antihormone therapy together with ipilimumab may kill more tumor cells.~PURPOSE: This randomized phase II trial is study how well giving hormone therapy and ipilimumab together works in treating patients with advanced prostate cancer.	OBJECTIVES:~I. To generally test whether the addition of CTLA-4 blockade can enhance clinical treatment response in advance prostate cancer patients compared with treatment with AA therapy alone.~II. To specifically examine whether concomitant AA therapy + MDX-010 can be used to prolong the progression-free interval in advanced prostate cancer patients compared with inductive short-term AA therapy alone.~III. To specifically examine whether concomitant AA therapy + MDX-010 can be used to enhance initial PSA responses in advanced prostate cancer patients compared with inductive short-term AA therapy alone.~IV. To specifically examine whether delayed MDX-010 can be used to induce PSA response in patients experiencing disease progression following cessation of short-term AA therapy.~V. To generally examine whether MDX-010 enhances host immune response that might be involved in conferring treatment advantages to patients receiving AA therapy.~VI. To specifically examine whether MDX-010 potentiates T-cell responses in advanced prostate cancer patients initiating inductive short-term AA therapy.~VII. To further examine whether treatment induced T-cell responses correlate with clinical response to treatment.~VIII. To examine whether short-term AA there (+/- MDX-010) induces the appearance of newly emigrated T or immature and/or B cells.~OUTLINE:~Patients are randomized to 1 of 2 treatment arms.~ARM I: Patients receive either leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) on days 0, 28, and 56. Patients also receive oral flutamide three times daily or oral bicalutamide once daily. Treatment with antiandrogen (AA) therapy continues for 3 months (3-4 months for patients who initiated AA therapy <= 21 days prior to enrollment) in the absence of disease progression or unacceptable toxicity. Patients receive ipilimumab IV over 90 minutes on day 7 (within 7-28 days post-initiation of AA therapy for patients who initiated AA therapy <= 21 days prior to enrollment) of AA therapy.~Arm II: Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression.~After completion of study treatment, patients are followed periodically.	A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy and CTLA-4 Blockade as a Treatment for Advanced Prostate Cancer	Prostate Adenocarcinoma, Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage III Prostate Cancer, Stage IV Prostate Cancer	* Drug: Bicalutamide * Drug: Flutamide * Drug: Goserelin Acetate * Drug: Ipilimumab * Drug: Leuprolide Acetate * Other: Pharmacological Study	Inclusion Criteria:~NOTE: All values must be obtained =< 14 prior to study entry~Histologically confirmed adenocarcinoma of the prostate staged within 180 days of study enrollment, >cT2cN0/M0 stage with or without metastatic disease, with the exclusion of central nervous system (CNS) metastases; includes post radical prostatectomy patients with a rising PSA~An initial PSA >= 4.0 ng/mL (Hybritech Assay)~For those patients who have received hormone therapy =< 21 days, a documented PSA of >= 4.0 prior to initiation of hormone therapy is acceptable.~For patients who are post radical prostatectomy, a rising PSA is acceptable.~Adequate organ function defined as: WBC >= 3,000/uL; platelets >= 75,000/uL; total bilirubin =< 1.5 mg/dL; transaminases =< 2.5 x upper limit of normal (ULN); serum creatine =< 2.0 mg/dL or calculated creatinine clearance >= 60 mL/min~ECOG performance status of 0-2~Able to understand and sign informed consent~Exclusion Criteria:~Underlying other serious medical condition which, in the opinion of the investigator precludes study participation; this includes immune-suppressive disease such as AIDS or autoimmune disorders such as multiple sclerosis, lupus, or myasthenia gravis~Patients not recovered from major infections and/or surgical procedures~Prior hormonal therapy > 21 days prior to enrollment, including estrogens, LH/RH agonists, or antiandrogens~Recent (=< 3 months of informed consent) usage of immune-suppressive medication including steroids, Immuran, Cyclosporin; topical or inhalational steroid use is permissible~Prior systemic chemotherapy~Prior radiation therapy to the prostate~Prior malignancy, unless the patient has been cancer-free for five years or more~Uncontrolled underlying medical or psychiatric illness, or serious active infections~Patient unwilling to complete all required follow-up visits~History of motor neuropathy considered of the autoimmune origin (e.g. Guillian-Barre Syndrome)~Concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer~For patients who elect to undergo the baseline transrectal needle biopsy of the prostate, current usage of systemic anticoagulation therapy, i.e. heparin or Coumadin or inability to discontinue aspirin, aspirin-containing products or ibuprofen for seven days prior to the prostate biopsies required for this study~No other investigational drugs will be allowed during the study~Other chemotherapy, radiation therapy, immunotherapy, hormonal therapy, or biologic therapy may not be used while the patient is on study	18 Years	null	Male	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants Progression-free at 18 Months \| PSA progression is defined as a rise in PSA to >4.0 ng/mL demonstrated twice in measurements taken two weeks apart. \| 18 months from the start of AA therapy \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response \| Percent of participants who had undetectable PSA at 3 months on the initially assigned treatment arm (prior to crossing over). \| 3 months \|		Ipilimumab, Leuprolide, Goserelin, Bicalutamide, Flutamide, Antineoplastic Agents, Immunological, Antineoplastic Agents, Immune Checkpoint Inhibitors, Molecular Mechanisms of Pharmacological Action, Fertility Agents, Female, Fertility Agents, Reproductive Control Agents, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal, Androgen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Arm I<br>Patients receive either leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) on days 0, 28, and 56. Patients also receive oral flutamide three times daily or oral bicalutamide once daily. Treatment with antiandrogen (AA) therapy continues for 3 months (3-4 months for patients who initiated AA therapy <= 21 days prior to enrollment) in the absence of disease progression or unacceptable toxicity. Patients receive ipilimumab IV over 90 minutes on day 7 (within 7-28 days post-initiation of AA therapy for patients who initiated AA therapy <= 21 days prior to enrollment) of AA therapy. \| Drug: Bicalutamide<br>* Given orally<br>* Other names: ICI 176334;Drug: Flutamide<br>* Given orally<br>* Other names: Testotard;Drug: Goserelin Acetate<br>* Given SC<br>* Other names: Zoladex;Drug: Ipilimumab<br>* Given IV<br>* Other names: Yervoy;Drug: Leuprolide Acetate<br>* Given IM<br>* Other names: Viadur;Other: Pharmacological Study<br>* Correlative study<br>\| \| Active Comparator: Arm II<br>Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression. \| Drug: Bicalutamide<br>* Given orally<br>* Other names: ICI 176334;Drug: Flutamide<br>* Given orally<br>* Other names: Testotard;Drug: Leuprolide Acetate<br>* Given IM<br>* Other names: Viadur;Other: Pharmacological Study<br>* Correlative study<br>\|	Hormone Therapy and Ipilimumab in Treating Patients With Advanced Prostate Cancer Study Overview ================= Brief Summary ----------------- RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin, flutamide, or bicalutamide may lessen the amount of androgens made by the body. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving antihormone therapy together with ipilimumab may kill more tumor cells. PURPOSE: This randomized phase II trial is study how well giving hormone therapy and ipilimumab together works in treating patients with advanced prostate cancer. Detailed Description ----------------- OBJECTIVES: I. To generally test whether the addition of CTLA-4 blockade can enhance clinical treatment response in advance prostate cancer patients compared with treatment with AA therapy alone. II. To specifically examine whether concomitant AA therapy + MDX-010 can be used to prolong the progression-free interval in advanced prostate cancer patients compared with inductive short-term AA therapy alone. III. To specifically examine whether concomitant AA therapy + MDX-010 can be used to enhance initial PSA responses in advanced prostate cancer patients compared with inductive short-term AA therapy alone. IV. To specifically examine whether delayed MDX-010 can be used to induce PSA response in patients experiencing disease progression following cessation of short-term AA therapy. V. To generally examine whether MDX-010 enhances host immune response that might be involved in conferring treatment advantages to patients receiving AA therapy. VI. To specifically examine whether MDX-010 potentiates T-cell responses in advanced prostate cancer patients initiating inductive short-term AA therapy. VII. To further examine whether treatment induced T-cell responses correlate with clinical response to treatment. VIII. To examine whether short-term AA there (+/- MDX-010) induces the appearance of newly emigrated T or immature and/or B cells. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive either leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) on days 0, 28, and 56. Patients also receive oral flutamide three times daily or oral bicalutamide once daily. Treatment with antiandrogen (AA) therapy continues for 3 months (3-4 months for patients who initiated AA therapy <= 21 days prior to enrollment) in the absence of disease progression or unacceptable toxicity. Patients receive ipilimumab IV over 90 minutes on day 7 (within 7-28 days post-initiation of AA therapy for patients who initiated AA therapy <= 21 days prior to enrollment) of AA therapy. Arm II: Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression. After completion of study treatment, patients are followed periodically. Official Title ----------------- A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy and CTLA-4 Blockade as a Treatment for Advanced Prostate Cancer Conditions ----------------- Prostate Adenocarcinoma, Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage III Prostate Cancer, Stage IV Prostate Cancer Intervention / Treatment ----------------- * Drug: Bicalutamide * Drug: Flutamide * Drug: Goserelin Acetate * Drug: Ipilimumab * Drug: Leuprolide Acetate * Other: Pharmacological Study Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: NOTE: All values must be obtained =< 14 prior to study entry Histologically confirmed adenocarcinoma of the prostate staged within 180 days of study enrollment, >cT2cN0/M0 stage with or without metastatic disease, with the exclusion of central nervous system (CNS) metastases; includes post radical prostatectomy patients with a rising PSA An initial PSA >= 4.0 ng/mL (Hybritech Assay) For those patients who have received hormone therapy =< 21 days, a documented PSA of >= 4.0 prior to initiation of hormone therapy is acceptable. For patients who are post radical prostatectomy, a rising PSA is acceptable. Adequate organ function defined as: WBC >= 3,000/uL; platelets >= 75,000/uL; total bilirubin =< 1.5 mg/dL; transaminases =< 2.5 x upper limit of normal (ULN); serum creatine =< 2.0 mg/dL or calculated creatinine clearance >= 60 mL/min ECOG performance status of 0-2 Able to understand and sign informed consent Exclusion Criteria: Underlying other serious medical condition which, in the opinion of the investigator precludes study participation; this includes immune-suppressive disease such as AIDS or autoimmune disorders such as multiple sclerosis, lupus, or myasthenia gravis Patients not recovered from major infections and/or surgical procedures Prior hormonal therapy > 21 days prior to enrollment, including estrogens, LH/RH agonists, or antiandrogens Recent (=< 3 months of informed consent) usage of immune-suppressive medication including steroids, Immuran, Cyclosporin; topical or inhalational steroid use is permissible Prior systemic chemotherapy Prior radiation therapy to the prostate Prior malignancy, unless the patient has been cancer-free for five years or more Uncontrolled underlying medical or psychiatric illness, or serious active infections Patient unwilling to complete all required follow-up visits History of motor neuropathy considered of the autoimmune origin (e.g. Guillian-Barre Syndrome) Concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer For patients who elect to undergo the baseline transrectal needle biopsy of the prostate, current usage of systemic anticoagulation therapy, i.e. heparin or Coumadin or inability to discontinue aspirin, aspirin-containing products or ibuprofen for seven days prior to the prostate biopsies required for this study No other investigational drugs will be allowed during the study Other chemotherapy, radiation therapy, immunotherapy, hormonal therapy, or biologic therapy may not be used while the patient is on study Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Arm I<br>Patients receive either leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) on days 0, 28, and 56. Patients also receive oral flutamide three times daily or oral bicalutamide once daily. Treatment with antiandrogen (AA) therapy continues for 3 months (3-4 months for patients who initiated AA therapy <= 21 days prior to enrollment) in the absence of disease progression or unacceptable toxicity. Patients receive ipilimumab IV over 90 minutes on day 7 (within 7-28 days post-initiation of AA therapy for patients who initiated AA therapy <= 21 days prior to enrollment) of AA therapy. \| Drug: Bicalutamide<br>* Given orally<br>* Other names: ICI 176334;Drug: Flutamide<br>* Given orally<br>* Other names: Testotard;Drug: Goserelin Acetate<br>* Given SC<br>* Other names: Zoladex;Drug: Ipilimumab<br>* Given IV<br>* Other names: Yervoy;Drug: Leuprolide Acetate<br>* Given IM<br>* Other names: Viadur;Other: Pharmacological Study<br>* Correlative study<br>\| \| Active Comparator: Arm II<br>Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression. \| Drug: Bicalutamide<br>* Given orally<br>* Other names: ICI 176334;Drug: Flutamide<br>* Given orally<br>* Other names: Testotard;Drug: Leuprolide Acetate<br>* Given IM<br>* Other names: Viadur;Other: Pharmacological Study<br>* Correlative study<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants Progression-free at 18 Months \| PSA progression is defined as a rise in PSA to >4.0 ng/mL demonstrated twice in measurements taken two weeks apart. \| 18 months from the start of AA therapy \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response \| Percent of participants who had undetectable PSA at 3 months on the initially assigned treatment arm (prior to crossing over). \| 3 months \|
NCT04083300	Cancer, Physical Activity and Quality of Life- a Longterm Follow up	This project is a 6-8-years follow-up of a randomized controlled trial testing a stepped care stress management program. The main goal is to examining differences in long-term effects on cancer-related stress reactions and emotional reactivity between the intervention and control group. Secondary objectives is to investigate consequences of cancer and its' treatment over time, such as long term quality of life, objectively physical activity and experiences concerning follow-up and the transition from specialist health services to municipal health services.	Major improvements in cancer detection and treatment lead to longer life expectancy among cancer survivors. This may in turn lead to more late effects and many have to deal with long-term consequences of the disease and its' treatment. Returning to everyday life and to work is often an important part of returning to normal life for cancer survivors. There is increasing knowledge concerning late effects, but there is still lack of knowledge concerning the life of those experiencing late effects. There is a need for more knowledge about late effects' impact on the return to work prosess, physical activity and quality of life over time. Both quantitative and qualitative methods will be utilized. Standardized questionnaires will provide information on the effect of the intervention over time, in addition to quality of life over time. Sensewear armband will provide information about their physical activity over time. Official register data from the Norwegian Labour and Welfare Administration (the NAV administration) will provide us information about the work- and benefit situation through the whole follow-up period of 6-8 years. The register data include information about type of social benefits (sick-leave benefit, work assessment allowance (WAA), disability pension, unemployment benefit and retirement pension), as well as information about occupation, income and sick leave diagnosis. Focus group interviews will give us insight in the cancer survivors own experiences with quality of life over time, the transition from the specialist health services to the primary health care and the follow-up in the municipalities.	6-8 Years Follow up of Cancer Survivors, Objectively Measured Physical Activity and Quality of Life Over Time.	Cancer, Rehabilitation, Stress Disorder, Fatigue, Quality of Life, Physical Activity		Inclusion Criteria:~Stage I-III disease~Scheduled for neo/adjuvant or curative treatment (i.e. chemotherapy, radiation therapy or hormonal therapy or any combination of these therapies)~Exclusion Criteria:~On-going psychiatric condition~Lack of fluency in Norwegian~A previous diagnosis of cancer	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cancer-related stress reactions 6-8 years after the diagnosis and inclusion in the study. \| \| 2021 \| \| Objectively measured physical activity from diagnosis to 6-8 years follow up. \| \| 2022 \| \| The context between change in physical activity and quality of life over time \| \| 2023 \| \| Witch predictors has an impact on long term cancer survivors quality of life? \| \| 2024 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cancer survivors' experience of quality of life 6-8 years after diagnosis- a qualitative study \| Experiences of the follow up. \| 2021 \|				Cancer, Physical Activity and Quality of Life- a Longterm Follow up Study Overview ================= Brief Summary ----------------- This project is a 6-8-years follow-up of a randomized controlled trial testing a stepped care stress management program. The main goal is to examining differences in long-term effects on cancer-related stress reactions and emotional reactivity between the intervention and control group. Secondary objectives is to investigate consequences of cancer and its' treatment over time, such as long term quality of life, objectively physical activity and experiences concerning follow-up and the transition from specialist health services to municipal health services. Detailed Description ----------------- Major improvements in cancer detection and treatment lead to longer life expectancy among cancer survivors. This may in turn lead to more late effects and many have to deal with long-term consequences of the disease and its' treatment. Returning to everyday life and to work is often an important part of returning to normal life for cancer survivors. There is increasing knowledge concerning late effects, but there is still lack of knowledge concerning the life of those experiencing late effects. There is a need for more knowledge about late effects' impact on the return to work prosess, physical activity and quality of life over time. Both quantitative and qualitative methods will be utilized. Standardized questionnaires will provide information on the effect of the intervention over time, in addition to quality of life over time. Sensewear armband will provide information about their physical activity over time. Official register data from the Norwegian Labour and Welfare Administration (the NAV administration) will provide us information about the work- and benefit situation through the whole follow-up period of 6-8 years. The register data include information about type of social benefits (sick-leave benefit, work assessment allowance (WAA), disability pension, unemployment benefit and retirement pension), as well as information about occupation, income and sick leave diagnosis. Focus group interviews will give us insight in the cancer survivors own experiences with quality of life over time, the transition from the specialist health services to the primary health care and the follow-up in the municipalities. Official Title ----------------- 6-8 Years Follow up of Cancer Survivors, Objectively Measured Physical Activity and Quality of Life Over Time. Conditions ----------------- Cancer, Rehabilitation, Stress Disorder, Fatigue, Quality of Life, Physical Activity Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Stage I-III disease Scheduled for neo/adjuvant or curative treatment (i.e. chemotherapy, radiation therapy or hormonal therapy or any combination of these therapies) Exclusion Criteria: On-going psychiatric condition Lack of fluency in Norwegian A previous diagnosis of cancer Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cancer-related stress reactions 6-8 years after the diagnosis and inclusion in the study. \| \| 2021 \| \| Objectively measured physical activity from diagnosis to 6-8 years follow up. \| \| 2022 \| \| The context between change in physical activity and quality of life over time \| \| 2023 \| \| Witch predictors has an impact on long term cancer survivors quality of life? \| \| 2024 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cancer survivors' experience of quality of life 6-8 years after diagnosis- a qualitative study \| Experiences of the follow up. \| 2021 \|
NCT04594265	Weight-Adjusted Dosing of 3-OHB in Patients With Chronic Heart Failure	We aim to investigate the hemodynamic effects of weight-adjusted dosing of ketone monoester en patients with chronic heart failure.		Weight-Adjusted Dosing of 3-OHB in Patients With Chronic Heart Failure	Ketosis, Heart Failure	* Dietary Supplement: KetoneAid KE4 Pro Monoester * Dietary Supplement: Science in Sport Go Enegy	Inclusion criteria: Chronic HF: NYHA class II-III, left ventricular ejection fraction (LVEF) <40%~Exclusion Criteria: Diabetes or HbA1c >48 mmol/mol, significant cardiac valve disease, severe stable angina pectoris, severe comorbidity as judged by the investigator, inability to give informed consent	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Patients are studied in a randomized single-blind cross-over design. Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cardiac Output (L/min) \| Change in Cardiac output measured by Swann-Ganz Catherization during study period, \| 3 hours - Area under the curve \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Left Ventricular Ejection Fraction \| Change in LVEF measured by echocardiography during study periode \| 3 hours - Area under the curve \| \| Blood Ketones \| Change in blood Ketones measured by venous blood samples \| 3 hours \| \| Blood pH \| Change in venous blood pH during the study period \| 3 hours \|	Hemodynamics	Heart Failure, Heart Diseases, Cardiovascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Ketone Monoester<br>Weight-adjusted dose of 3-OHB Monoester (KetoneAID KE4, Virginia, US) 0.5 g/kg (max 50 g) \| Dietary Supplement: KetoneAid KE4 Pro Monoester<br>* A dietary supplement containing ketone monoester.<br>\| \| Placebo Comparator: Placebo Treatment<br>Maltodextrin-based placebo (Science In Sport, UK) in isocaloric dose to the experimental arm. \| Dietary Supplement: Science in Sport Go Enegy<br>* Dosis isocaloric to the KetoneAid Arm<br>\| \| Active Comparator: Ketone Monoester in presence of low-dose insulin clamp<br>Same as experimental arm, but in the presence of a low-dose insulin clamp to suppress free fatty acid metabolism \| Dietary Supplement: KetoneAid KE4 Pro Monoester<br>* A dietary supplement containing ketone monoester.<br>\|	Weight-Adjusted Dosing of 3-OHB in Patients With Chronic Heart Failure Study Overview ================= Brief Summary ----------------- We aim to investigate the hemodynamic effects of weight-adjusted dosing of ketone monoester en patients with chronic heart failure. Official Title ----------------- Weight-Adjusted Dosing of 3-OHB in Patients With Chronic Heart Failure Conditions ----------------- Ketosis, Heart Failure Intervention / Treatment ----------------- * Dietary Supplement: KetoneAid KE4 Pro Monoester * Dietary Supplement: Science in Sport Go Enegy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: Chronic HF: NYHA class II-III, left ventricular ejection fraction (LVEF) <40% Exclusion Criteria: Diabetes or HbA1c >48 mmol/mol, significant cardiac valve disease, severe stable angina pectoris, severe comorbidity as judged by the investigator, inability to give informed consent Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Patients are studied in a randomized single-blind cross-over design. Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Ketone Monoester<br>Weight-adjusted dose of 3-OHB Monoester (KetoneAID KE4, Virginia, US) 0.5 g/kg (max 50 g) \| Dietary Supplement: KetoneAid KE4 Pro Monoester<br>* A dietary supplement containing ketone monoester.<br>\| \| Placebo Comparator: Placebo Treatment<br>Maltodextrin-based placebo (Science In Sport, UK) in isocaloric dose to the experimental arm. \| Dietary Supplement: Science in Sport Go Enegy<br>* Dosis isocaloric to the KetoneAid Arm<br>\| \| Active Comparator: Ketone Monoester in presence of low-dose insulin clamp<br>Same as experimental arm, but in the presence of a low-dose insulin clamp to suppress free fatty acid metabolism \| Dietary Supplement: KetoneAid KE4 Pro Monoester<br>* A dietary supplement containing ketone monoester.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cardiac Output (L/min) \| Change in Cardiac output measured by Swann-Ganz Catherization during study period, \| 3 hours - Area under the curve \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Left Ventricular Ejection Fraction \| Change in LVEF measured by echocardiography during study periode \| 3 hours - Area under the curve \| \| Blood Ketones \| Change in blood Ketones measured by venous blood samples \| 3 hours \| \| Blood pH \| Change in venous blood pH during the study period \| 3 hours \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Hemodynamics
NCT00805831	Safety and Efficacy of Using HDH Device and Method - a Novel Sutureless Vascular Anastomosis	The HDH device is intended for creating sutureless vascular anastomosis in various blood vessels. The HDH device consists of four parts: an elastic tube (graft), docking head (anastomotic device), inversion device (connects the vascular graft to HDH) and measuring device. This study was design in order to evaluate the safety and efficacy of using HDH device and method an innovative anastomotic device for sutureless aortic anastomosis in patient diagnosed with abdominal aneurysm or Aorto-iliac aneurysm.		Safety and Efficacy of Using HDH Device and Method - a Novel Sutureless Vascular Anastomosis	Vascular Disease, Atherosclerosis	* Device: HDH	Inclusion Criteria:~Patient age above 18 (men and woman)~Patient suffers from infrarenal abdominal aortic or Aorto-iliac aneurysm~Aneurysm diameter is larger than 5cm/ its annual growth is more than 0.5cm/or iliac aneurysm size is larger than 2.5cm~The abdominal aneurysm neck is longer than 1.5 cm~Patient's physical condition allows performing general anesthesia~Patient is willing to sign the informed consent and follow the study protocol.~Exclusion Criteria:~Patient Age under 18 years~Patient's physical condition dose not allows to perform general anesthesia~Patient's with terminal disease and life expectancy of less than 3 months~Patient objects to the treatment or study protocol~Anesthesiologist or personal care physician object~Patient suffer from Supra/infrarenal AAA~The abdominal aneurysm neck is smaller than 1.5 cm~Aneurysm diameter is smaller than 5cm/ its annual growth is less than 0.5cm/	18 Years	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| To establish safety of using the HDH device for creating sutureless aortic anastomosis. Safety will be established by lack of serious adverse events. \| \| within 1 month \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time to complete the anastomosis \| \| during the surgery \|	sutureless vascular bypass	Atherosclerosis, Vascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Cardiovascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: A<br>Aortic anastomosis surgery will be conducted using HDH device. \| Device: HDH<br>* sutureless vascular anastomosis<br>\|	Safety and Efficacy of Using HDH Device and Method - a Novel Sutureless Vascular Anastomosis Study Overview ================= Brief Summary ----------------- The HDH device is intended for creating sutureless vascular anastomosis in various blood vessels. The HDH device consists of four parts: an elastic tube (graft), docking head (anastomotic device), inversion device (connects the vascular graft to HDH) and measuring device. This study was design in order to evaluate the safety and efficacy of using HDH device and method an innovative anastomotic device for sutureless aortic anastomosis in patient diagnosed with abdominal aneurysm or Aorto-iliac aneurysm. Official Title ----------------- Safety and Efficacy of Using HDH Device and Method - a Novel Sutureless Vascular Anastomosis Conditions ----------------- Vascular Disease, Atherosclerosis Intervention / Treatment ----------------- * Device: HDH Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient age above 18 (men and woman) Patient suffers from infrarenal abdominal aortic or Aorto-iliac aneurysm Aneurysm diameter is larger than 5cm/ its annual growth is more than 0.5cm/or iliac aneurysm size is larger than 2.5cm The abdominal aneurysm neck is longer than 1.5 cm Patient's physical condition allows performing general anesthesia Patient is willing to sign the informed consent and follow the study protocol. Exclusion Criteria: Patient Age under 18 years Patient's physical condition dose not allows to perform general anesthesia Patient's with terminal disease and life expectancy of less than 3 months Patient objects to the treatment or study protocol Anesthesiologist or personal care physician object Patient suffer from Supra/infrarenal AAA The abdominal aneurysm neck is smaller than 1.5 cm Aneurysm diameter is smaller than 5cm/ its annual growth is less than 0.5cm/ Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: A<br>Aortic anastomosis surgery will be conducted using HDH device. \| Device: HDH<br>* sutureless vascular anastomosis<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| To establish safety of using the HDH device for creating sutureless aortic anastomosis. Safety will be established by lack of serious adverse events. \| \| within 1 month \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time to complete the anastomosis \| \| during the surgery \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- sutureless vascular bypass
NCT00606606	Reducing Adverse Drug Events in the Nursing Home	Medications are the single most common form of treatment in the long-term care setting, and often represent the most efficacious (and cost-effective) therapeutic modality used in this clinical setting. However, the residents of nursing homes are at increased risk for experiencing adverse drug events. This risk is increased by the physiologic decline and pharmacologic changes that occur with aging, and also by the special clinical and social circumstances that characterize institutional long-term care. In a study funded by the National Institute on Aging (AG 14472), we have previously determined that adverse drug events are common and often preventable in the nursing home setting and that the more serious the adverse drug event, the more likely it is to be preventable. This study will test whether a computer-based clinical decision support system can lower the rate of adverse drug events (ADEs) and potential ADEs in the long-term care setting. The study design is a randomized trial based in the resident care units of two large long-term care facilities. Within each facility, half of the resident care units will be randomized to an intervention arm receiving the computer-based clinical decision support system which will display warnings, messages, and prompts based on resident and drug use characteristics; with over-rides by the prescriber required for some warnings. Rates of ADEs and potential ADEs will be tracked by the study's on-site clinical pharmacists prior to and during the intervention period. Rates will be compared between units receiving and not receiving the computer¬based clinical decision support system and to baseline, pre-intervention rates in the same units. We will track all project costs directly related to the development and installation of the computer-based clinical decision support system. We will also develop and test the sensitivity and specificity of a computerized adverse drug event monitor and assess the validity of a nursing home resident risk model developed in our prior study of adverse drug events in the nursing home setting.	This study was conducted in two large, academic long-term care facilities located in Connecticut and Ontario, Canada. The two facilities have a combined total of 1,229 beds. Patients residing in areas of the facilities related to short-term care (e.g., subacute care, hospital-level care, or rehabilitation) were not included in the study population.~Each of the facilities had an existing computerized provider order entry system without a computer-based clinical decision support system. At the time of the study, approximately 90% of new medication orders were entered using the system. All medication prescribing was performed by contracted staff; in one of the study facilities this included 27 physicians, nurse practitioners, and physicians' assistants. In the other facility, medication prescribing was performed by 10 physicians.~Across the two long-term care facilities, 26 resident care units, each with existing computer provider order entry, were randomized to having a clinical decision support system (intervention units) or not (control units). Bed size of the resident care units ranged from 20 to 60 beds. An effort was made to match the units according to bed size and general characteristics of the residents on the units. We block randomized within categories including: dementia units, units where mental health and behavioral problems were common among the residents, units where the residents had complex medical needs, and units where the residents had profound deficits in physical function.~On intervention units, prescribers ordering drugs were presented with alerts in the form of warning messages; these alerts were not displayed to prescribers when ordering medications for residents of control units. Although efforts were initially made to limit crossover of prescribers between intervention and control units, over the duration of the study, there were providers working simultaneously on both types of units, both on a temporary (coverage) basis and also permanently.~The clinical decision support system was designed by a team of geriatricians, pharmacists, health services researchers, and information system specialists; the process of developing the clinical decision support system and its components has been described previously. The design principles were: 1) messages should be evidence-based; 2) messages should be perceived as useful and informative by practitioners; and 3) the system should have only modest impact on the time required for the practitioner to complete an order. The team reviewed the types of preventable adverse drug events based on previous research, as well as widely accepted published criteria for suboptimal prescribing in the elderly available at the time of this study. We also reviewed all serious drug-drug interactions from standard pharmaceutical drug interaction databases and included alerts for a limited number of more than 600 potentially serious interactions that were reviewed. Reasons for exclusion of alerts for specific drug interactions included that the medications were not on formulary at the facility, or that the medications were generally never used in elderly patients or in the long-term care setting.~The clinical decision support system was designed to provide alerts in response to selected drug orders whenever the order: 1) involved selected high-severity drug interactions; 2) was for a patient with selected abnormal lab test results that suggested a possible danger related to use of the ordered medication; 3) could lead to adverse effects that require special monitoring in order to identify them early; 4) related to a medication that should be ordered within certain dose ranges to reduce the risk of adverse effects in elderly patients; or 5) should be accompanied by prophylactic measures to proactively address situations where there was a high likelihood of adverse drug effects (e.g., constipation with opioid use). Alerts included specific instructions for laboratory monitoring, as well as less explicit recommendations for reconsidering drug orders and monitoring for possible side effects. A summary of the alerts is provided in the appendix.~The computerized provider order entry system in place at the time of the clinical decision support system implementation was capable of linking laboratory test orders and results and current drug orders in real-time. However, the system had several important limitations, as described previously. It was not capable of combining dose and strength information to determine the total daily dose associated with a drug order; therefore, some alerts displayed when they may not have been necessary (e.g., the medication order was already within the recommended dose range). The underlying software was not capable of distinguishing multiple orders for the same drug in different forms or strengths, or orders that had been cancelled and re-ordered within the same prescribing session. These orders were interpreted as multiple orders for drugs in the same category and triggered a number of inappropriate alerts about drug interactions. For example, an order for erythromycin that the prescriber initiated, cancelled, and then re-ordered within the same ordering session would be interpreted as an interaction signaling the need for an alert for increased risk of QT prolongation. Despite the fact that some triggers were likely to produce a substantial number of these unnecessary alerts, we opted to include them in the system if the potential impact of the type of drug interaction in question was considered clinically important.~For residents on the intervention units, the alerts were displayed in a pop-up box to prescribers in real-time when a drug order was entered. The pop-up boxes were informational; they did not require specific actions from the prescriber and did not produce or revise orders automatically. On the control units, the alerts were not displayed to the prescribers.~Our study was limited to adverse drug events occurring in the long-term care setting. Drug-related incidents were identified through review of medical records in monthly segments performed by trained pharmacist investigators for each eligible long-term care facility resident. These investigators, who were not aware of whether the resident was located on an intervention or a control unit, examined the records for possible drug-related incidents, such as new symptoms or events that might represent an adverse drug event, changes in medication regimens (including acute discontinuations or initiations of medications that might be used to treat a drug-induced event), abnormal laboratory values, and all emergency room transfers and hospitalizations. In addition to periodic reviews, medical records were specially targeted for review based on information derived from selected computer-generated signals including abnormal serum drug levels, abnormal laboratory results, and the use of medications considered to be antidotes for adverse drug effects. Administrative incident reports generated within each participating facility were also reviewed for any indication of a drug-related incident.~The primary outcome of the study was an adverse drug event, defined as an injury resulting from the use of a drug. This definition is consistent with definitions used in previous studies. Adverse drug events may have resulted from medication errors (e.g., errors in ordering, dispensing, administration, and monitoring) or from adverse drug reactions in which there was no error.~As described previously, the between-pharmacist investigator reliability for identifying relevant incidents in medical records was assessed through independent review of the same 10 medical records by each of the two pharmacists. Each identified the same incident in the 10 medical records; one pharmacist identified an additional incident in one record that had not been pre-specified as an incident warranting review.~The possible drug-related incidents were presented by a pharmacist investigator to pairs of physician-reviewers (JHG, JJ, PR, LRH, and CB). These physician-reviewers independently classified incidents using structured implicit review according to the following criteria: whether an adverse drug event was present, the severity of the event, and whether the event was preventable. In determining whether an adverse drug event had occurred, the physician-reviewers considered the temporal relation between the drug exposure and the event, as well as whether the event reflected a known effect of the drug. This structured implicit review process has been used in numerous prior studies relating to adverse drug events across various clinical settings. Physician reviewers were not aware of whether a drug-related incident being reviewed had occurred in a resident of an intervention or a control unit.~The severity of adverse events was categorized as less serious, serious, life-threatening, or fatal. Adverse drug events categorized as less serious included a non-urticarial skin rash, a fall without associated fracture, hemorrhage not requiring transfusion or hospitalization, and oversedation. Examples of events categorized as serious included urticaria, falls with associated fracture, hemorrhage requiring transfusion or hospitalization but without hypotension, and delirium. Examples of life-threatening events include hemorrhage with associated hypotension, hypoglycemic encephalopathy, and acute renal failure. Adverse drug events were considered to be preventable if they were judged to be due to an error and were preventable by any means available and not just in relation to the clinical decision support system. For the purpose of the analysis of the effect of the intervention, any event characterized as serious or greater in severity, was categorized as more severe. All other events were considered less severe.~Preventability was categorized as preventable, probably preventable, probably not preventable, or definitely not preventable; results were collapsed into preventable (preventable and probably preventable) and nonpreventable (probably not preventable and definitely not preventable) categories in the analysis.~When the physician-reviewers disagreed on the classification of an incident regarding the presence of an adverse drug event, its severity, or its preventability, they met and reached consensus; consensus was reached in all instances where there was initial disagreement.	Reducing Adverse Drug Events in the Nursing Home	Adverse Drug Events	* Other: Clinical Decision Support	Inclusion Criteria:~prescriber at the study facilities~Exclusion Criteria:~not a prescriber at the study facilities	null	null	All	Accepts Healthy Volunteers	Primary Purpose: Health Services Research Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| adverse drug events \| \| March 2002 - February 2005 \|			Drug-Related Side Effects and Adverse Reactions, Chemically-Induced Disorders	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: I - Intervention units<br>nursing home units, provided HIT CDS intervention \| Other: Clinical Decision Support<br> <br> * Other names: CDS;\| \| No Intervention: C - control units<br>nursing home units, not provided the HIT CDS intervention \| \|	Reducing Adverse Drug Events in the Nursing Home Study Overview ================= Brief Summary ----------------- Medications are the single most common form of treatment in the long-term care setting, and often represent the most efficacious (and cost-effective) therapeutic modality used in this clinical setting. However, the residents of nursing homes are at increased risk for experiencing adverse drug events. This risk is increased by the physiologic decline and pharmacologic changes that occur with aging, and also by the special clinical and social circumstances that characterize institutional long-term care. In a study funded by the National Institute on Aging (AG 14472), we have previously determined that adverse drug events are common and often preventable in the nursing home setting and that the more serious the adverse drug event, the more likely it is to be preventable. This study will test whether a computer-based clinical decision support system can lower the rate of adverse drug events (ADEs) and potential ADEs in the long-term care setting. The study design is a randomized trial based in the resident care units of two large long-term care facilities. Within each facility, half of the resident care units will be randomized to an intervention arm receiving the computer-based clinical decision support system which will display warnings, messages, and prompts based on resident and drug use characteristics; with over-rides by the prescriber required for some warnings. Rates of ADEs and potential ADEs will be tracked by the study's on-site clinical pharmacists prior to and during the intervention period. Rates will be compared between units receiving and not receiving the computer¬based clinical decision support system and to baseline, pre-intervention rates in the same units. We will track all project costs directly related to the development and installation of the computer-based clinical decision support system. We will also develop and test the sensitivity and specificity of a computerized adverse drug event monitor and assess the validity of a nursing home resident risk model developed in our prior study of adverse drug events in the nursing home setting. Detailed Description ----------------- This study was conducted in two large, academic long-term care facilities located in Connecticut and Ontario, Canada. The two facilities have a combined total of 1,229 beds. Patients residing in areas of the facilities related to short-term care (e.g., subacute care, hospital-level care, or rehabilitation) were not included in the study population. Each of the facilities had an existing computerized provider order entry system without a computer-based clinical decision support system. At the time of the study, approximately 90% of new medication orders were entered using the system. All medication prescribing was performed by contracted staff; in one of the study facilities this included 27 physicians, nurse practitioners, and physicians' assistants. In the other facility, medication prescribing was performed by 10 physicians. Across the two long-term care facilities, 26 resident care units, each with existing computer provider order entry, were randomized to having a clinical decision support system (intervention units) or not (control units). Bed size of the resident care units ranged from 20 to 60 beds. An effort was made to match the units according to bed size and general characteristics of the residents on the units. We block randomized within categories including: dementia units, units where mental health and behavioral problems were common among the residents, units where the residents had complex medical needs, and units where the residents had profound deficits in physical function. On intervention units, prescribers ordering drugs were presented with alerts in the form of warning messages; these alerts were not displayed to prescribers when ordering medications for residents of control units. Although efforts were initially made to limit crossover of prescribers between intervention and control units, over the duration of the study, there were providers working simultaneously on both types of units, both on a temporary (coverage) basis and also permanently. The clinical decision support system was designed by a team of geriatricians, pharmacists, health services researchers, and information system specialists; the process of developing the clinical decision support system and its components has been described previously. The design principles were: 1) messages should be evidence-based; 2) messages should be perceived as useful and informative by practitioners; and 3) the system should have only modest impact on the time required for the practitioner to complete an order. The team reviewed the types of preventable adverse drug events based on previous research, as well as widely accepted published criteria for suboptimal prescribing in the elderly available at the time of this study. We also reviewed all serious drug-drug interactions from standard pharmaceutical drug interaction databases and included alerts for a limited number of more than 600 potentially serious interactions that were reviewed. Reasons for exclusion of alerts for specific drug interactions included that the medications were not on formulary at the facility, or that the medications were generally never used in elderly patients or in the long-term care setting. The clinical decision support system was designed to provide alerts in response to selected drug orders whenever the order: 1) involved selected high-severity drug interactions; 2) was for a patient with selected abnormal lab test results that suggested a possible danger related to use of the ordered medication; 3) could lead to adverse effects that require special monitoring in order to identify them early; 4) related to a medication that should be ordered within certain dose ranges to reduce the risk of adverse effects in elderly patients; or 5) should be accompanied by prophylactic measures to proactively address situations where there was a high likelihood of adverse drug effects (e.g., constipation with opioid use). Alerts included specific instructions for laboratory monitoring, as well as less explicit recommendations for reconsidering drug orders and monitoring for possible side effects. A summary of the alerts is provided in the appendix. The computerized provider order entry system in place at the time of the clinical decision support system implementation was capable of linking laboratory test orders and results and current drug orders in real-time. However, the system had several important limitations, as described previously. It was not capable of combining dose and strength information to determine the total daily dose associated with a drug order; therefore, some alerts displayed when they may not have been necessary (e.g., the medication order was already within the recommended dose range). The underlying software was not capable of distinguishing multiple orders for the same drug in different forms or strengths, or orders that had been cancelled and re-ordered within the same prescribing session. These orders were interpreted as multiple orders for drugs in the same category and triggered a number of inappropriate alerts about drug interactions. For example, an order for erythromycin that the prescriber initiated, cancelled, and then re-ordered within the same ordering session would be interpreted as an interaction signaling the need for an alert for increased risk of QT prolongation. Despite the fact that some triggers were likely to produce a substantial number of these unnecessary alerts, we opted to include them in the system if the potential impact of the type of drug interaction in question was considered clinically important. For residents on the intervention units, the alerts were displayed in a pop-up box to prescribers in real-time when a drug order was entered. The pop-up boxes were informational; they did not require specific actions from the prescriber and did not produce or revise orders automatically. On the control units, the alerts were not displayed to the prescribers. Our study was limited to adverse drug events occurring in the long-term care setting. Drug-related incidents were identified through review of medical records in monthly segments performed by trained pharmacist investigators for each eligible long-term care facility resident. These investigators, who were not aware of whether the resident was located on an intervention or a control unit, examined the records for possible drug-related incidents, such as new symptoms or events that might represent an adverse drug event, changes in medication regimens (including acute discontinuations or initiations of medications that might be used to treat a drug-induced event), abnormal laboratory values, and all emergency room transfers and hospitalizations. In addition to periodic reviews, medical records were specially targeted for review based on information derived from selected computer-generated signals including abnormal serum drug levels, abnormal laboratory results, and the use of medications considered to be antidotes for adverse drug effects. Administrative incident reports generated within each participating facility were also reviewed for any indication of a drug-related incident. The primary outcome of the study was an adverse drug event, defined as an injury resulting from the use of a drug. This definition is consistent with definitions used in previous studies. Adverse drug events may have resulted from medication errors (e.g., errors in ordering, dispensing, administration, and monitoring) or from adverse drug reactions in which there was no error. As described previously, the between-pharmacist investigator reliability for identifying relevant incidents in medical records was assessed through independent review of the same 10 medical records by each of the two pharmacists. Each identified the same incident in the 10 medical records; one pharmacist identified an additional incident in one record that had not been pre-specified as an incident warranting review. The possible drug-related incidents were presented by a pharmacist investigator to pairs of physician-reviewers (JHG, JJ, PR, LRH, and CB). These physician-reviewers independently classified incidents using structured implicit review according to the following criteria: whether an adverse drug event was present, the severity of the event, and whether the event was preventable. In determining whether an adverse drug event had occurred, the physician-reviewers considered the temporal relation between the drug exposure and the event, as well as whether the event reflected a known effect of the drug. This structured implicit review process has been used in numerous prior studies relating to adverse drug events across various clinical settings. Physician reviewers were not aware of whether a drug-related incident being reviewed had occurred in a resident of an intervention or a control unit. The severity of adverse events was categorized as less serious, serious, life-threatening, or fatal. Adverse drug events categorized as less serious included a non-urticarial skin rash, a fall without associated fracture, hemorrhage not requiring transfusion or hospitalization, and oversedation. Examples of events categorized as serious included urticaria, falls with associated fracture, hemorrhage requiring transfusion or hospitalization but without hypotension, and delirium. Examples of life-threatening events include hemorrhage with associated hypotension, hypoglycemic encephalopathy, and acute renal failure. Adverse drug events were considered to be preventable if they were judged to be due to an error and were preventable by any means available and not just in relation to the clinical decision support system. For the purpose of the analysis of the effect of the intervention, any event characterized as serious or greater in severity, was categorized as more severe. All other events were considered less severe. Preventability was categorized as preventable, probably preventable, probably not preventable, or definitely not preventable; results were collapsed into preventable (preventable and probably preventable) and nonpreventable (probably not preventable and definitely not preventable) categories in the analysis. When the physician-reviewers disagreed on the classification of an incident regarding the presence of an adverse drug event, its severity, or its preventability, they met and reached consensus; consensus was reached in all instances where there was initial disagreement. Official Title ----------------- Reducing Adverse Drug Events in the Nursing Home Conditions ----------------- Adverse Drug Events Intervention / Treatment ----------------- * Other: Clinical Decision Support Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: prescriber at the study facilities Exclusion Criteria: not a prescriber at the study facilities Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Health Services Research Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: I - Intervention units<br>nursing home units, provided HIT CDS intervention \| Other: Clinical Decision Support<br> <br> * Other names: CDS;\| \| No Intervention: C - control units<br>nursing home units, not provided the HIT CDS intervention \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| adverse drug events \| \| March 2002 - February 2005 \|
NCT02328339	Tea and Forearm Blood Flow	The study will explore the benefit of tea for microcirculation. Subjects will consume tea ar a placebo matched for taste and appearance in a blinded cross over design.	Epidemiological studies indicate that regular consumption of black tea reduces the risk of cardiovascular diseases. Tea consumption can result in improvements in endothelial function of conduit arteries as measured by flow mediated dilation.~Less is known however about its effects in other vascular beds. The study will test the hypothesis that tea affects endothelial function in the muscle microcirculation. This will be done by assessment of forearm blood flow using venous occlusion plethysmography after consumption of black tea against or placebo in a randomised, full cross-over study in 20 healthy middle-aged to elderly subjects	Forearm Blood Flow Response to Acute Consumption of Black Tea	Vascular Function	* Other: Tea * Other: Placebo	Inclusion Criteria:~Males and post menopausal (> 1 years) females~Aged ≥ 45 and ≤ 75 years~Body mass index (BMI) of ≥ 18.0 and ≤ 35.0 kg/m2~Judged to be in good health on the basis of medical history, physical examination and routine laboratory tests (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, highly sensitive C-reactive protein).~Normal blood coagulation as assessed by routine lab tests~Exclusion Criteria:~Strenuous exercise > 2 hours per week. Strenuous exercise is defined as exercise which induces sweating and causes sufficient breathlessness to limit conversation~Current smoker or has stopped smoking less than 6 months before start of study~Self reported alcohol intake of > 21 units/week)~Established cardiovascular disease or clinically significant arrhythmia~Diabetes mellitus~Blood pressure > 160/100 mmHg~Taking medication that might affect endothelial function (as judged by the PI)	45 Years	75 Years	All	Accepts Healthy Volunteers	Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Forearm blood flow response to acetylcholine \| Does tea ingestion change mean forearm blood flow response to acetylcholine when compared to placebo \| During acetylcholine infusion 120-140 min after first tea/placebo intake \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Forearm blood flow response to sodium nitropusside \| Does tea ingestion change mean forearm blood flow response to sodium nitropusside when compared to placebo \| During sodium nitropusside infusion 170-190 min after first tea/placebo intake \| \| Forearm blood flow response to L-NMMA \| Does tea ingestion change mean forearm blood flow response to L-NG-monomethyl Arginine (L-NMMA) when compared to placebo \| During L-NMMA infusion 220-240 min after first tea/placebo intake \|			\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Black tea<br>Approximately 400 mg total polyphenols in 240 ml hot water (loading dose; 2 hours before the start of measurements; t=0) and 130 mg total polyphenols in 120 ml hot water (maintenance dose just before start of the measurements; t=120 min) \| Other: Tea<br>* Black tea infusion equivalent to approximately 530 mg total polyphenols expressed as gallic acid equivalents<br>\| \| Placebo Comparator: Placebo<br>Caramel colour, maltodextrin and tea flavour in 240 ml hot water (2 hours before the start of measurements; t=0) and 120 ml hot water (maintenance dose just before start of the measurements; t=120 min) \| Other: Placebo<br>* Placebo matched to tea with respect to taste and appearance<br>\|	Tea and Forearm Blood Flow Study Overview ================= Brief Summary ----------------- The study will explore the benefit of tea for microcirculation. Subjects will consume tea ar a placebo matched for taste and appearance in a blinded cross over design. Detailed Description ----------------- Epidemiological studies indicate that regular consumption of black tea reduces the risk of cardiovascular diseases. Tea consumption can result in improvements in endothelial function of conduit arteries as measured by flow mediated dilation. Less is known however about its effects in other vascular beds. The study will test the hypothesis that tea affects endothelial function in the muscle microcirculation. This will be done by assessment of forearm blood flow using venous occlusion plethysmography after consumption of black tea against or placebo in a randomised, full cross-over study in 20 healthy middle-aged to elderly subjects Official Title ----------------- Forearm Blood Flow Response to Acute Consumption of Black Tea Conditions ----------------- Vascular Function Intervention / Treatment ----------------- * Other: Tea * Other: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Males and post menopausal (> 1 years) females Aged ≥ 45 and ≤ 75 years Body mass index (BMI) of ≥ 18.0 and ≤ 35.0 kg/m2 Judged to be in good health on the basis of medical history, physical examination and routine laboratory tests (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, highly sensitive C-reactive protein). Normal blood coagulation as assessed by routine lab tests Exclusion Criteria: Strenuous exercise > 2 hours per week. Strenuous exercise is defined as exercise which induces sweating and causes sufficient breathlessness to limit conversation Current smoker or has stopped smoking less than 6 months before start of study Self reported alcohol intake of > 21 units/week) Established cardiovascular disease or clinically significant arrhythmia Diabetes mellitus Blood pressure > 160/100 mmHg Taking medication that might affect endothelial function (as judged by the PI) Ages Eligible for Study ----------------- Minimum Age: 45 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Black tea<br>Approximately 400 mg total polyphenols in 240 ml hot water (loading dose; 2 hours before the start of measurements; t=0) and 130 mg total polyphenols in 120 ml hot water (maintenance dose just before start of the measurements; t=120 min) \| Other: Tea<br>* Black tea infusion equivalent to approximately 530 mg total polyphenols expressed as gallic acid equivalents<br>\| \| Placebo Comparator: Placebo<br>Caramel colour, maltodextrin and tea flavour in 240 ml hot water (2 hours before the start of measurements; t=0) and 120 ml hot water (maintenance dose just before start of the measurements; t=120 min) \| Other: Placebo<br>* Placebo matched to tea with respect to taste and appearance<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Forearm blood flow response to acetylcholine \| Does tea ingestion change mean forearm blood flow response to acetylcholine when compared to placebo \| During acetylcholine infusion 120-140 min after first tea/placebo intake \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Forearm blood flow response to sodium nitropusside \| Does tea ingestion change mean forearm blood flow response to sodium nitropusside when compared to placebo \| During sodium nitropusside infusion 170-190 min after first tea/placebo intake \| \| Forearm blood flow response to L-NMMA \| Does tea ingestion change mean forearm blood flow response to L-NG-monomethyl Arginine (L-NMMA) when compared to placebo \| During L-NMMA infusion 220-240 min after first tea/placebo intake \|
NCT04711629	Clinical Features of Smoker Patients With Chronic Obstructive Pulmonary Disease	Smoking is the most important factor in the etiology of COPD. Some of the patients with COPD continue to smoke despite knowing this situation or they cannot quit even if they want.~The aim of this study is; To examine patients with COPD who continue to smoke in terms of perception of dyspnea, exercise capacity, psychological symptoms and quality of life.	The study was designed prospectively. Patients with COPD who apply to the pulmonary rehabilitation outpatient clinic will be included.~The data of patients with COPD who are eligible for PR and have been pre-evaluated will be scanned. Respiratory function test, arterial blood gas analysis, six-minute walking test (6-MWT), mMRC Dyspnea Scale, St George Quality of Life Questionnaire and Hospital Anxiety Depression Scale will be used in the study. Patients with COPD who smoke will constitute the study group, and those who quit smoking will constitute the control group.	Clinical Characteristics of Chronic Obstructive Pulmonary Patients Who Continue to Smoke	Copd, Smoking	* Other: Clinical Tests	Inclusion Criteria:~Smoker COPD Patients who smoker~Exclusion Criteria:~Not volunteer to participate the study	18 Years	90 Years	All	Accepts Healthy Volunteers	Primary Purpose: Supportive Care Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: Smoker COPD Ex Smoker COPD Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Exercise Capacity \| Six minutes walk test \| 6 minutes \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Respiratory Functions \| Pulmonary Function Test Pulmonary function test (PFT) which is noninvasive tests that show how well the lungs are working. The tests will measure FEV1; It is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration.~FVC: It s the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry FEV1/FVC: It represents the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC). \| 30 minutes \| \| Dyspnea Sensation \| Modified Medical Research Council (MMRC) dyspnea scale, which consists of 5 items ranging between 1 and 5, to determine the severity of patients' shortness of breath. \| 20 minutes \| \| Disease Specific Quality of Life \| St. George's Respiratory Questionnaire (SGRQ) to determine disease-specific quality of life. At this scale, high scores define worsened disease and increased symptoms. \| 20 minutes \| \| Anxiety \| Hospital Anxiety and Depression (HAD) Inventory for assessment of anxiety and depression. In this scale; scores of anxiety and depression are calculated separately. The maximum score for both is 21 and high scores correspond to high degree anxiety and depression. Cut-off scores for anxiety and depression were determined as 10/11 and 7/8 respectively. \| 20 minutes \| \| Depression \| Hospital Anxiety and Depression (HAD) Inventory for assessment of anxiety and depression. In this scale; scores of anxiety and depression are calculated separately. The maximum score for both is 21 and high scores correspond to high degree anxiety and depression. Cut-off scores for anxiety and depression were determined as 10/11 and 7/8 respectively. \| 20 minutes \| \| Body Mass Index \| Body mass index is calculated by dividing body mass by the square of length in meters. \| 5 minutes \|	copd, smoking		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Smoker COPD<br>Patients who continue to smoke \| Other: Clinical Tests<br>* Respiratory function test, arterial blood gas analysis, six-minute walking test (6-MWT), mMRC Dyspnea Scale, St George Quality of Life Questionnaire and Hospital Anxiety Depression Scale<br>\| \| Active Comparator: Ex-smoker COPD<br>Patients who quit smoking. \| Other: Clinical Tests<br>* Respiratory function test, arterial blood gas analysis, six-minute walking test (6-MWT), mMRC Dyspnea Scale, St George Quality of Life Questionnaire and Hospital Anxiety Depression Scale<br>\|	Clinical Features of Smoker Patients With Chronic Obstructive Pulmonary Disease Study Overview ================= Brief Summary ----------------- Smoking is the most important factor in the etiology of COPD. Some of the patients with COPD continue to smoke despite knowing this situation or they cannot quit even if they want. The aim of this study is; To examine patients with COPD who continue to smoke in terms of perception of dyspnea, exercise capacity, psychological symptoms and quality of life. Detailed Description ----------------- The study was designed prospectively. Patients with COPD who apply to the pulmonary rehabilitation outpatient clinic will be included. The data of patients with COPD who are eligible for PR and have been pre-evaluated will be scanned. Respiratory function test, arterial blood gas analysis, six-minute walking test (6-MWT), mMRC Dyspnea Scale, St George Quality of Life Questionnaire and Hospital Anxiety Depression Scale will be used in the study. Patients with COPD who smoke will constitute the study group, and those who quit smoking will constitute the control group. Official Title ----------------- Clinical Characteristics of Chronic Obstructive Pulmonary Patients Who Continue to Smoke Conditions ----------------- Copd, Smoking Intervention / Treatment ----------------- * Other: Clinical Tests Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Smoker COPD Patients who smoker Exclusion Criteria: Not volunteer to participate the study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 90 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: Smoker COPD Ex Smoker COPD Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Smoker COPD<br>Patients who continue to smoke \| Other: Clinical Tests<br>* Respiratory function test, arterial blood gas analysis, six-minute walking test (6-MWT), mMRC Dyspnea Scale, St George Quality of Life Questionnaire and Hospital Anxiety Depression Scale<br>\| \| Active Comparator: Ex-smoker COPD<br>Patients who quit smoking. \| Other: Clinical Tests<br>* Respiratory function test, arterial blood gas analysis, six-minute walking test (6-MWT), mMRC Dyspnea Scale, St George Quality of Life Questionnaire and Hospital Anxiety Depression Scale<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Exercise Capacity \| Six minutes walk test \| 6 minutes \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Respiratory Functions \| Pulmonary Function Test Pulmonary function test (PFT) which is noninvasive tests that show how well the lungs are working. The tests will measure FEV1; It is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration. FVC: It s the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry FEV1/FVC: It represents the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC). \| 30 minutes \| \| Dyspnea Sensation \| Modified Medical Research Council (MMRC) dyspnea scale, which consists of 5 items ranging between 1 and 5, to determine the severity of patients' shortness of breath. \| 20 minutes \| \| Disease Specific Quality of Life \| St. George's Respiratory Questionnaire (SGRQ) to determine disease-specific quality of life. At this scale, high scores define worsened disease and increased symptoms. \| 20 minutes \| \| Anxiety \| Hospital Anxiety and Depression (HAD) Inventory for assessment of anxiety and depression. In this scale; scores of anxiety and depression are calculated separately. The maximum score for both is 21 and high scores correspond to high degree anxiety and depression. Cut-off scores for anxiety and depression were determined as 10/11 and 7/8 respectively. \| 20 minutes \| \| Depression \| Hospital Anxiety and Depression (HAD) Inventory for assessment of anxiety and depression. In this scale; scores of anxiety and depression are calculated separately. The maximum score for both is 21 and high scores correspond to high degree anxiety and depression. Cut-off scores for anxiety and depression were determined as 10/11 and 7/8 respectively. \| 20 minutes \| \| Body Mass Index \| Body mass index is calculated by dividing body mass by the square of length in meters. \| 5 minutes \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- copd, smoking
NCT04535986	A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD	The purpose of this study is to evaluate the efficacy and safety of ensifentrine in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).		A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine Over 24 Weeks (With a 48-week Safety Subset) in Subjects With Moderate to Severe COPD	Chronic Obstructive Pulmonary Disease	* Drug: Ensifentrine * Drug: Placebo	Inclusion Criteria:~Informed Consent~Capable of giving informed consent indicating that they understand the purpose of the study and study procedures and agree to comply with the requirements and restrictions listed in the informed consent form (ICF).~Age and Sex~Age: Patient must be 40 to 80 years of age inclusive, at the time of Screening.~Sex:~Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.~Females are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions apply:~Not a woman of childbearing potential (WOCBP) as defined in Or~A WOCBP who agrees to follow the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.~Smoking History~Smoking History: Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years at Screening (Visit 0) [number of pack years = (number of cigarettes per day / 20) × number of years smoked (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 0. Smoking cessation programs are permitted during the study.~COPD Diagnosis, Symptoms, Severity and Maintenance Therapy~COPD Diagnosis: Patients with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD.~COPD Symptoms: A score of ≥2 on the Modified Medical Research Council (mMRC) Dyspnea Scale.~COPD Severity:~Pre- and Post-albuterol/salbutamol FEV1/FVC ratio of <0.70.~Post-albuterol/salbutamol FEV1 ≥30 % and ≤70% of predicted normal calculated using the National Health and Nutrition Examination Survey III.~Maintenance Therapy: Patients on no maintenance/background therapy or patients on stable maintenance LAMA or LABA therapy are eligible. Patients taking maintenance LAMA or LABA therapy must demonstrate stable use of the maintenance LAMA or LABA therapy for at least 3 months prior to Screening and agree to continue use for the duration of the study. Background maintenance LAMA or LABA bronchodilator therapy will be capped at 50% of patients.~Other Requirements for Inclusion~Capable of withholding SABAs for 4 hours prior to initiation of any spirometry. Patients in the maintenance LAMA or LABA therapy stratum must be capable of withholding Twice-Daily maintenance LAMA or LABA for 24 hours and Once-Daily maintenance LAMA or LABA for 48 hours prior to initiation of any spirometry.~Capable of using the study nebulizer correctly and complying with all study restrictions and procedures.~Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines.~Inclusion Criteria at Randomization (RPL554-CO-301)~Symptoms of COPD: A score of ≥2 on the mMRC Dyspnea Scale.~Completion of the e-Diary at least 5 of the last 7 days of the Run-in period.~Exclusion Criteria:~Current Condition or Medical History~History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.~Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening and/or a positive COVID-19 test result indicating an active infection at Screening. Patients with COVID-19 antibodies from a previous exposure with no active infection are not excluded.~COPD exacerbation requiring oral or parenteral steroids within 3 months of Screening.~Previous lung resection or lung reduction surgery within 1-year of Screening.~Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day. As needed oxygen use (≤12 hours per day) is not exclusionary.~Pulmonary rehabilitation, unless such treatment has been in a stable maintenance phase for 4 weeks prior to Visit 1 and remains stable during the study.~Lower respiratory tract infection within 6 weeks of Screening.~Other respiratory disorders including, but not limited to, a current diagnosis of asthma, active tuberculosis, lung cancer, sarcoidosis, lung fibrosis, interstitial lung diseases, unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary diseases.~Major surgery (requiring general anesthesia) in the 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.~Historical or current evidence of clinically significant cardiovascular disease defined as any disease that in the opinion of the Investigator would put the safety of the patient at risk through participation or which could affect the efficacy or safety analysis if the disease/condition were to exacerbate during the study, including, but not limited to:~Myocardial infarction or unstable angina within 6 months prior to Screening.~Unstable or life-threatening cardiac arrhythmia requiring intervention within 3 months prior to Screening.~Diagnosis of New York Heart Association Class III and Class IV heart failure.~Chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant.~Unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).~History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin.~Findings on physical examination that an investigator considers to be clinically significant at Screening.~Prior/Concomitant Therapy~Use of prohibited medications within the time intervals.~History or Suspicion of Drug or Alcohol Abuse~Current or history of past drug or alcohol abuse within the past 5 years.~Laboratory and Other Diagnostic Parameters~Glomerular Filtration Rate (eGFR) <30 mL/min. The Chronic Kidney Disease Epidemiology Collaboration Creatinine (2009) calculation will be used (Levey, 2009).~Alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).~Any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal. Abnormal chemistry and/or hematology may be repeated during Screening.~Chest X-ray (CXR; posterior-anterior) at Screening, or in the 12 months prior to Screening with clinically significant abnormalities not attributable to COPD. If a CXR within the past 12 months is not available but a computerized tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR. For subjects in Germany, if a CXR or CT scan is not available in the 12 months prior to Screening, the subject is not eligible for the study.~Electrocardiogram (ECG) finding that is significantly abnormal on the 12-lead ECG obtained at Screening.~Other Exclusions~Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days prior to Screening.~Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days prior to Screening.~Intolerance or hypersensitivity to albuterol/salbutamol or ensifentrine (RPL554) or any of its excipients/components.~Prior receipt of blinded study medication in an ensifentrine (RPL554) study.~Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned.~Inability to read, understand, and/or complete questionnaires (in the opinion of the Investigator).~A disclosed history or one known to the Investigator of significant non-compliance in previous investigational studies or with prescribed medications.~Any other reason that the Investigator considers makes the patient unsuitable to participate.~Exclusion Criteria at Randomization (RPL554-CO-301)~COPD exacerbation or lower respiratory tract infection between Screening and Randomization (defined as use of any additional treatment other than current treatment and rescue medication and/or emergency department or hospital visit). Patients with a severe COPD exacerbation that requires hospitalization may not be rescreened.~Positive COVID-19 result at Screening or between Screening and Randomization.~Prohibited medication use between Screening Visit 0 and Visit 1.~Significantly abnormal ECG finding on the 12-lead ECG obtained at Screening as assessed by the investigator or site medical doctor/medically qualified person or on the pre-dose (prior to randomization) ECG obtained at Visit 1.~In the event that the central ECG reviewer discovers a significant ECG abnormality on the Visit 1 ECG, the patient will be discontinued.~Did not meet one or more of the Inclusion Criteria or met one or more of the Exclusion Criteria.	40 Years	80 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Least Square (LS) Mean Change From Baseline in Average Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) at Week 12 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-12h was defined as AUC over 12 hours of the FEV1, divided by 12 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. \| Baseline (pre-dose on Day 1) and Week 12 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| LS Mean Change From Baseline FEV1 to Peak FEV1 at Day 1 and Weeks 6, 12 and 24 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Peak FEV1 is the maximum value in the 4 hours after dosing. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline to the Mean Weekly Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24 \| The E-RS scale consists of 11 questions, with 3 sub-domains of: breathlessness, cough and sputum, and chest symptoms. The E-RS sub-domain score was calculated as the sum from the relevant questions. The E-RS total score was derived as the sum of the raw scores of the 11 items ranging from 0 to 40. Higher scores indicates severe respiratory symptoms. Scores were derived weekly as the mean over 7 days prior to the visit, using only days where data was recorded. The E-RS was collected daily by electronic diary (e-diary). Baseline is the mean over the 7 days prior to the first intake of study medication, using only days where data was recorded. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 6, 12 and 24 \| The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Score ranging from 0 to 100 and higher scores indicated a worse outcome. Baseline is the score calculated on Day 1 prior to 4 hour post-dose spirometry. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline FEV1 to Morning Trough FEV1 at Weeks 6, 12 and 24 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Morning trough FEV1 was the last value collected prior to the morning dose. Baseline FEV1 is the mean of the two measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline in Average FEV1 Area Under the Curve Over 4 Hours (AUC0-4h) at Day 1 and Weeks 6, 12 and 24 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-4h was defined as area under the curve over 4 hours of the FEV1, divided by 4 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24 \| \| Percentage of SGRQ Responders at Weeks 6, 12 and 24 \| The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Responder was a patient with an improvement from baseline in SGRQ total score of 4 or more. Percentage of SGRQ responders are reported. \| Weeks 6, 12 and 24 \| \| LS Mean Change From Baseline to the Mean Weekly Rescue Medication Use at Weeks 6, 12 and 24 \| Use of rescue medication (albuterol/salbutamol) per week was calculated as the LS mean use daily over 7 days. Daily rescue medication use was collected in an e-diary throughout the study. Baseline is the mean over the 7 days prior to the first intake of study medication, calculated as the sum of puffs taken, divided by number of days data has been recorded. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Transition Dyspnea Index (TDI) Questionnaire Total Score at Weeks 6, 12 and 24 \| The TDI is a questionnaire that focused on 3 sub-domains: functional impairment, magnitude of task and magnitude of effort. Sub-domain score was calculated as the sum from the related questions. Total score was calculated as the sum of the sub-domain scores. The TDI measures the change in dyspnea severity from the baseline as measured by the baseline dyspnea index. It was rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement). Higher scores indicate better outcome. Change from baseline was assessed with the Baseline Dyspnea Index. \| Weeks 6, 12 and 24 \| \| LS Mean Change From Baseline FEV1 to Evening Trough FEV1 at Week 12 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Evening trough FEV1 was the value collected at 12 hours post-morning dose and prior to the evening dose. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1) and Week 12 \|	COPD	Lung Diseases, Obstructive, Pulmonary Disease, Chronic Obstructive, Lung Diseases, Respiratory Tract Diseases, Chronic Disease, Disease Attributes, Pathologic Processes	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Arm 1<br>Ensifentrine Nebulized Suspension; 3 mg BID \| Drug: Ensifentrine<br>* Dosage Formulation: Ensifentrine Nebulizer suspension Dosage 3mg Frequency: Twice Daily for 24 weeks or 48 weeks<br>\| \| Placebo Comparator: Arm 2<br>Placebo Nebulized BID \| Drug: Placebo<br>* Dosage Formulation: Ensifentrine Placebo Nebulizer solution Frequency: Twice Daily for 24 weeks or 48 weeks<br>\|	A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate the efficacy and safety of ensifentrine in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD). Official Title ----------------- A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine Over 24 Weeks (With a 48-week Safety Subset) in Subjects With Moderate to Severe COPD Conditions ----------------- Chronic Obstructive Pulmonary Disease Intervention / Treatment ----------------- * Drug: Ensifentrine * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Informed Consent Capable of giving informed consent indicating that they understand the purpose of the study and study procedures and agree to comply with the requirements and restrictions listed in the informed consent form (ICF). Age and Sex Age: Patient must be 40 to 80 years of age inclusive, at the time of Screening. Sex: Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication. Females are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions apply: Not a woman of childbearing potential (WOCBP) as defined in Or A WOCBP who agrees to follow the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication. Smoking History Smoking History: Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years at Screening (Visit 0) [number of pack years = (number of cigarettes per day / 20) × number of years smoked (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 0. Smoking cessation programs are permitted during the study. COPD Diagnosis, Symptoms, Severity and Maintenance Therapy COPD Diagnosis: Patients with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD. COPD Symptoms: A score of ≥2 on the Modified Medical Research Council (mMRC) Dyspnea Scale. COPD Severity: Pre- and Post-albuterol/salbutamol FEV1/FVC ratio of <0.70. Post-albuterol/salbutamol FEV1 ≥30 % and ≤70% of predicted normal calculated using the National Health and Nutrition Examination Survey III. Maintenance Therapy: Patients on no maintenance/background therapy or patients on stable maintenance LAMA or LABA therapy are eligible. Patients taking maintenance LAMA or LABA therapy must demonstrate stable use of the maintenance LAMA or LABA therapy for at least 3 months prior to Screening and agree to continue use for the duration of the study. Background maintenance LAMA or LABA bronchodilator therapy will be capped at 50% of patients. Other Requirements for Inclusion Capable of withholding SABAs for 4 hours prior to initiation of any spirometry. Patients in the maintenance LAMA or LABA therapy stratum must be capable of withholding Twice-Daily maintenance LAMA or LABA for 24 hours and Once-Daily maintenance LAMA or LABA for 48 hours prior to initiation of any spirometry. Capable of using the study nebulizer correctly and complying with all study restrictions and procedures. Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines. Inclusion Criteria at Randomization (RPL554-CO-301) Symptoms of COPD: A score of ≥2 on the mMRC Dyspnea Scale. Completion of the e-Diary at least 5 of the last 7 days of the Run-in period. Exclusion Criteria: Current Condition or Medical History History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation. Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening and/or a positive COVID-19 test result indicating an active infection at Screening. Patients with COVID-19 antibodies from a previous exposure with no active infection are not excluded. COPD exacerbation requiring oral or parenteral steroids within 3 months of Screening. Previous lung resection or lung reduction surgery within 1-year of Screening. Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day. As needed oxygen use (≤12 hours per day) is not exclusionary. Pulmonary rehabilitation, unless such treatment has been in a stable maintenance phase for 4 weeks prior to Visit 1 and remains stable during the study. Lower respiratory tract infection within 6 weeks of Screening. Other respiratory disorders including, but not limited to, a current diagnosis of asthma, active tuberculosis, lung cancer, sarcoidosis, lung fibrosis, interstitial lung diseases, unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary diseases. Major surgery (requiring general anesthesia) in the 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study. Historical or current evidence of clinically significant cardiovascular disease defined as any disease that in the opinion of the Investigator would put the safety of the patient at risk through participation or which could affect the efficacy or safety analysis if the disease/condition were to exacerbate during the study, including, but not limited to: Myocardial infarction or unstable angina within 6 months prior to Screening. Unstable or life-threatening cardiac arrhythmia requiring intervention within 3 months prior to Screening. Diagnosis of New York Heart Association Class III and Class IV heart failure. Chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant. Unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones). History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin. Findings on physical examination that an investigator considers to be clinically significant at Screening. Prior/Concomitant Therapy Use of prohibited medications within the time intervals. History or Suspicion of Drug or Alcohol Abuse Current or history of past drug or alcohol abuse within the past 5 years. Laboratory and Other Diagnostic Parameters Glomerular Filtration Rate (eGFR) <30 mL/min. The Chronic Kidney Disease Epidemiology Collaboration Creatinine (2009) calculation will be used (Levey, 2009). Alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal. Abnormal chemistry and/or hematology may be repeated during Screening. Chest X-ray (CXR; posterior-anterior) at Screening, or in the 12 months prior to Screening with clinically significant abnormalities not attributable to COPD. If a CXR within the past 12 months is not available but a computerized tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR. For subjects in Germany, if a CXR or CT scan is not available in the 12 months prior to Screening, the subject is not eligible for the study. Electrocardiogram (ECG) finding that is significantly abnormal on the 12-lead ECG obtained at Screening. Other Exclusions Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days prior to Screening. Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days prior to Screening. Intolerance or hypersensitivity to albuterol/salbutamol or ensifentrine (RPL554) or any of its excipients/components. Prior receipt of blinded study medication in an ensifentrine (RPL554) study. Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned. Inability to read, understand, and/or complete questionnaires (in the opinion of the Investigator). A disclosed history or one known to the Investigator of significant non-compliance in previous investigational studies or with prescribed medications. Any other reason that the Investigator considers makes the patient unsuitable to participate. Exclusion Criteria at Randomization (RPL554-CO-301) COPD exacerbation or lower respiratory tract infection between Screening and Randomization (defined as use of any additional treatment other than current treatment and rescue medication and/or emergency department or hospital visit). Patients with a severe COPD exacerbation that requires hospitalization may not be rescreened. Positive COVID-19 result at Screening or between Screening and Randomization. Prohibited medication use between Screening Visit 0 and Visit 1. Significantly abnormal ECG finding on the 12-lead ECG obtained at Screening as assessed by the investigator or site medical doctor/medically qualified person or on the pre-dose (prior to randomization) ECG obtained at Visit 1. In the event that the central ECG reviewer discovers a significant ECG abnormality on the Visit 1 ECG, the patient will be discontinued. Did not meet one or more of the Inclusion Criteria or met one or more of the Exclusion Criteria. Ages Eligible for Study ----------------- Minimum Age: 40 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Arm 1<br>Ensifentrine Nebulized Suspension; 3 mg BID \| Drug: Ensifentrine<br>* Dosage Formulation: Ensifentrine Nebulizer suspension Dosage 3mg Frequency: Twice Daily for 24 weeks or 48 weeks<br>\| \| Placebo Comparator: Arm 2<br>Placebo Nebulized BID \| Drug: Placebo<br>* Dosage Formulation: Ensifentrine Placebo Nebulizer solution Frequency: Twice Daily for 24 weeks or 48 weeks<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Least Square (LS) Mean Change From Baseline in Average Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) at Week 12 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-12h was defined as AUC over 12 hours of the FEV1, divided by 12 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. \| Baseline (pre-dose on Day 1) and Week 12 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| LS Mean Change From Baseline FEV1 to Peak FEV1 at Day 1 and Weeks 6, 12 and 24 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Peak FEV1 is the maximum value in the 4 hours after dosing. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline to the Mean Weekly Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24 \| The E-RS scale consists of 11 questions, with 3 sub-domains of: breathlessness, cough and sputum, and chest symptoms. The E-RS sub-domain score was calculated as the sum from the relevant questions. The E-RS total score was derived as the sum of the raw scores of the 11 items ranging from 0 to 40. Higher scores indicates severe respiratory symptoms. Scores were derived weekly as the mean over 7 days prior to the visit, using only days where data was recorded. The E-RS was collected daily by electronic diary (e-diary). Baseline is the mean over the 7 days prior to the first intake of study medication, using only days where data was recorded. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 6, 12 and 24 \| The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Score ranging from 0 to 100 and higher scores indicated a worse outcome. Baseline is the score calculated on Day 1 prior to 4 hour post-dose spirometry. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline FEV1 to Morning Trough FEV1 at Weeks 6, 12 and 24 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Morning trough FEV1 was the last value collected prior to the morning dose. Baseline FEV1 is the mean of the two measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Change From Baseline in Average FEV1 Area Under the Curve Over 4 Hours (AUC0-4h) at Day 1 and Weeks 6, 12 and 24 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-4h was defined as area under the curve over 4 hours of the FEV1, divided by 4 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24 \| \| Percentage of SGRQ Responders at Weeks 6, 12 and 24 \| The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Responder was a patient with an improvement from baseline in SGRQ total score of 4 or more. Percentage of SGRQ responders are reported. \| Weeks 6, 12 and 24 \| \| LS Mean Change From Baseline to the Mean Weekly Rescue Medication Use at Weeks 6, 12 and 24 \| Use of rescue medication (albuterol/salbutamol) per week was calculated as the LS mean use daily over 7 days. Daily rescue medication use was collected in an e-diary throughout the study. Baseline is the mean over the 7 days prior to the first intake of study medication, calculated as the sum of puffs taken, divided by number of days data has been recorded. \| Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24 \| \| LS Mean Transition Dyspnea Index (TDI) Questionnaire Total Score at Weeks 6, 12 and 24 \| The TDI is a questionnaire that focused on 3 sub-domains: functional impairment, magnitude of task and magnitude of effort. Sub-domain score was calculated as the sum from the related questions. Total score was calculated as the sum of the sub-domain scores. The TDI measures the change in dyspnea severity from the baseline as measured by the baseline dyspnea index. It was rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement). Higher scores indicate better outcome. Change from baseline was assessed with the Baseline Dyspnea Index. \| Weeks 6, 12 and 24 \| \| LS Mean Change From Baseline FEV1 to Evening Trough FEV1 at Week 12 \| Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Evening trough FEV1 was the value collected at 12 hours post-morning dose and prior to the evening dose. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, <=40 minutes pre-dose on day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines. \| Baseline (pre-dose on Day 1) and Week 12 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- COPD
NCT00126451	A Clinical Trial of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Relapsed or Refractory Breast, Colorectal and Non-Small Cell Lung Cancer (0683-011)(TERMINATED)	This is an investigational study to determine the response rate of relapsed/refractory breast, colorectal and non-small cell lung cancer to oral suberoylanilide hydroxamic acid (SAHA), to evaluate PET as an earlier indicator of response to SAHA as assessed by response evaluation criteria in solid tumours (RECIST) criteria and to evaluate the safety and tolerability of oral suberoylanilide hydroxamic acid.		A Phase II Clinical Study of Oral Suberoylanilide Hydroxamic Acid in Patients With Relapsed or Refractory Breast, Colorectal, and Non-small Cell Lung Cancer.	Breast Cancer, Colorectal Cancer, Non-small-cell Lung Carcinoma	* Drug: MK0683, vorinostat, Suberoylanilide Hydroxamic Acid (SAHA) * Drug: Duration of Treatment - During each treatment cycle, treatment is administered twice daily for 14 days, followed by 7 days of rest for a total of 10 cycles	Inclusion Criteria:~Patient must be 18 years or older with confirmed diagnosis of breast adenocarcinoma, colorectal carcinoma or non-small cell lung cancer~Patients must have relapsed or refractory disease following at least one chemotherapeutic treatment regimen.~Has a measurable, positron emission tomography (PET) assessable lesion~Adequate blood, liver, bone marrow and kidney functions~Has not received any chemotherapy for at least 4 weeks prior to entry in this study~Agrees to take adequate measures to prevent pregnancy.~Exclusion Criteria:~Patient has had prior treatment with histone deacetylase (HDAC) inhibitor.~Patient has had treatment with investigational agents within the last 30 days.~Patient has active infection or had intravenous (IV) antibiotic, antiviral, or antifungal medications within 2 weeks of the start of study drugs.~Patient has HIV, hepatitis B or hepatitis C infection.~Patient is pregnant or lactating.~Patient has allergy to any component of the study drug.	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Response rate of relapsed/refractory breast, colorectal and non-small cell lung cancer to SAHA using RECIST criteria. \| \| \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Positron emission tomography (PET) as an earlier indicator of the response to SAHA as assessed by RECIST criteria. To evaluate the safety and tolerability of SAHA for 14 days every 21 days. \| \| \|		Vorinostat, Antineoplastic Agents, Histone Deacetylase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action	\| Intervention/Treatment \| \| --- \| \|Drug: MK0683, vorinostat, Suberoylanilide Hydroxamic Acid (SAHA)\|nan\| \|Drug: Duration of Treatment - During each treatment cycle, treatment is administered twice daily for 14 days, followed by 7 days of rest for a total of 10 cycles\|nan\|	A Clinical Trial of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Relapsed or Refractory Breast, Colorectal and Non-Small Cell Lung Cancer (0683-011)(TERMINATED) Study Overview ================= Brief Summary ----------------- This is an investigational study to determine the response rate of relapsed/refractory breast, colorectal and non-small cell lung cancer to oral suberoylanilide hydroxamic acid (SAHA), to evaluate PET as an earlier indicator of response to SAHA as assessed by response evaluation criteria in solid tumours (RECIST) criteria and to evaluate the safety and tolerability of oral suberoylanilide hydroxamic acid. Official Title ----------------- A Phase II Clinical Study of Oral Suberoylanilide Hydroxamic Acid in Patients With Relapsed or Refractory Breast, Colorectal, and Non-small Cell Lung Cancer. Conditions ----------------- Breast Cancer, Colorectal Cancer, Non-small-cell Lung Carcinoma Intervention / Treatment ----------------- * Drug: MK0683, vorinostat, Suberoylanilide Hydroxamic Acid (SAHA) * Drug: Duration of Treatment - During each treatment cycle, treatment is administered twice daily for 14 days, followed by 7 days of rest for a total of 10 cycles Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient must be 18 years or older with confirmed diagnosis of breast adenocarcinoma, colorectal carcinoma or non-small cell lung cancer Patients must have relapsed or refractory disease following at least one chemotherapeutic treatment regimen. Has a measurable, positron emission tomography (PET) assessable lesion Adequate blood, liver, bone marrow and kidney functions Has not received any chemotherapy for at least 4 weeks prior to entry in this study Agrees to take adequate measures to prevent pregnancy. Exclusion Criteria: Patient has had prior treatment with histone deacetylase (HDAC) inhibitor. Patient has had treatment with investigational agents within the last 30 days. Patient has active infection or had intravenous (IV) antibiotic, antiviral, or antifungal medications within 2 weeks of the start of study drugs. Patient has HIV, hepatitis B or hepatitis C infection. Patient is pregnant or lactating. Patient has allergy to any component of the study drug. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: MK0683, vorinostat, Suberoylanilide Hydroxamic Acid (SAHA)\|nan\| \|Drug: Duration of Treatment - During each treatment cycle, treatment is administered twice daily for 14 days, followed by 7 days of rest for a total of 10 cycles\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Response rate of relapsed/refractory breast, colorectal and non-small cell lung cancer to SAHA using RECIST criteria. \| \| \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Positron emission tomography (PET) as an earlier indicator of the response to SAHA as assessed by RECIST criteria. To evaluate the safety and tolerability of SAHA for 14 days every 21 days. \| \| \|
NCT03637088	Acute Exposure of Simulated Hypoxia on Pulmonary Artery Pressure and Right Heart Function (Echo)	Randomized crossover trial in patients with Pulmonary Hypertension (PAH, CTEPH) to assess the acute response to simulated altitude (FiO2:15.1, equivalent to 2500m above sea level) on pulmonary artery pressure and right heart function (Echo).	Low altitude baseline measurements will be performed in Zurich (460m asl) including Echocardiography, Right heart catheterization, (six-minute walk test) 6MWT, pulmonary function test, clinical assessment and blood gas Analysis.~Randomly assigned to the order of testing, the participants will be tested under simulated altitude (FiO2: 15.1% with the AMC Altitrainer) and shamed altitude with the same device.~Several times within the exposure, the pulmonary artery pressure and the right heart function will be assessed by echo.	Acute Exposure to Hypoxia in Precapillary Pulmonary Hypertension: Physiological and Clinical Effects at Rest and During Exercise	Pulmonary Hypertension	* Device: Simulated Altitude (FiO2: 15.1%) * Device: Shamed Hypoxia (FiO2: 20.9)	Inclusion Criteria:~Informed consent~PH diagnosed according to internation Guidelines: mean pulmonary artery pressure (mPAP) ≥ 25 mmHg along with a (pulmonary artery wedge pressure) PAWP ≤15 mmHg during right heart catheterization at the time of initial diagnosis~PH class 1 (PAH) or 4 (CTEPH)~Stable condition, on the same medication for > 4 weeks~Patient live permanently at an altitude < 1000m asl.~Exclusion Criteria:~Resting partial Oxygen pressure (PaO2) ≤7.3 kilopascal (kPA) corresponding to the requirement of long-term oxygen therapy > 16hour daily (nocturnal oxygen therapy alone is allowed)~Severe daytime hypercapnia (pCO2 > 6.5 kPa)~Susceptibility to high altitude related diseases (AMS, high-altitude pulmonary edema (HAPE), etc.) based on previous experienced discomfort at altitudes.~Exposure to an altitude >1500m for ≥3 nights during the last 4 weeks before the study participation~Residence > 1000m above sea level~Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, neurological or orthopedic problems with walking disability~Women who are pregnant or breast feeding	18 Years	null	All	No	Primary Purpose: Prevention Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Including a baseline assessment and assessments under simulated altitude and normoxia. Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Echocardiographic assessment under hypoxia (FiO2: 15.1) \| Pulmonary artery pressure measured by echo (TTE) \| 2 hours \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Echocardiographic assessment of the right heart under hypoxia (FiO2: 15.1) \| Right heart functions measured by echo (TTE) (fac, d-shaping, kinetic etc.) \| 2 hours \|	Simulated altitude, Pulmonary artery pressure, Echocardiography, Right heart function	Hypertension, Pulmonary, Hypertension, Hypoxia, Vascular Diseases, Cardiovascular Diseases, Lung Diseases, Respiratory Tract Diseases, Signs and Symptoms, Respiratory	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Order air-hypoxia<br>The participants will be exposed to shamed hypoxia (FiO2: 20.9% equivalent to sea level and consecutively to simulated altitude (FiO2: 15.1% equivalent to 2500m above sea level) administered by an altitude Simulator (Altitrainer, SMTEC), simulated altitude (FiO2: 15.1%), with a facemask. \| Device: Simulated Altitude (FiO2: 15.1%)<br>* Inhalation of deoxygenated air through a altitude simulator (Altitrainer), for approx. 1 hour. given by a facemask.<br>Device: Shamed Hypoxia (FiO2: 20.9)<br>* Inhalation of unmodified air through an altitude simulator (Altitrainer) for approximately 1 hour given by a facemask<br>\| \| Experimental: Order hypoxia-air<br>The participant will be exposed to hypoxia (FiO2, 15.1% equivalent to 2500m above sea level), simulated altitude (FiO2: 15.1%), and consecutively to shamed hypoxia (FiO2, 20.9%) administered by an altitude simulator (Altitrainer, SMTEC) with a facemask. \| Device: Simulated Altitude (FiO2: 15.1%)<br>* Inhalation of deoxygenated air through a altitude simulator (Altitrainer), for approx. 1 hour. given by a facemask.<br>Device: Shamed Hypoxia (FiO2: 20.9)<br>* Inhalation of unmodified air through an altitude simulator (Altitrainer) for approximately 1 hour given by a facemask<br>\|	Acute Exposure of Simulated Hypoxia on Pulmonary Artery Pressure and Right Heart Function (Echo) Study Overview ================= Brief Summary ----------------- Randomized crossover trial in patients with Pulmonary Hypertension (PAH, CTEPH) to assess the acute response to simulated altitude (FiO2:15.1, equivalent to 2500m above sea level) on pulmonary artery pressure and right heart function (Echo). Detailed Description ----------------- Low altitude baseline measurements will be performed in Zurich (460m asl) including Echocardiography, Right heart catheterization, (six-minute walk test) 6MWT, pulmonary function test, clinical assessment and blood gas Analysis. Randomly assigned to the order of testing, the participants will be tested under simulated altitude (FiO2: 15.1% with the AMC Altitrainer) and shamed altitude with the same device. Several times within the exposure, the pulmonary artery pressure and the right heart function will be assessed by echo. Official Title ----------------- Acute Exposure to Hypoxia in Precapillary Pulmonary Hypertension: Physiological and Clinical Effects at Rest and During Exercise Conditions ----------------- Pulmonary Hypertension Intervention / Treatment ----------------- * Device: Simulated Altitude (FiO2: 15.1%) * Device: Shamed Hypoxia (FiO2: 20.9) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Informed consent PH diagnosed according to internation Guidelines: mean pulmonary artery pressure (mPAP) ≥ 25 mmHg along with a (pulmonary artery wedge pressure) PAWP ≤15 mmHg during right heart catheterization at the time of initial diagnosis PH class 1 (PAH) or 4 (CTEPH) Stable condition, on the same medication for > 4 weeks Patient live permanently at an altitude < 1000m asl. Exclusion Criteria: Resting partial Oxygen pressure (PaO2) ≤7.3 kilopascal (kPA) corresponding to the requirement of long-term oxygen therapy > 16hour daily (nocturnal oxygen therapy alone is allowed) Severe daytime hypercapnia (pCO2 > 6.5 kPa) Susceptibility to high altitude related diseases (AMS, high-altitude pulmonary edema (HAPE), etc.) based on previous experienced discomfort at altitudes. Exposure to an altitude >1500m for ≥3 nights during the last 4 weeks before the study participation Residence > 1000m above sea level Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, neurological or orthopedic problems with walking disability Women who are pregnant or breast feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Including a baseline assessment and assessments under simulated altitude and normoxia. Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Order air-hypoxia<br>The participants will be exposed to shamed hypoxia (FiO2: 20.9% equivalent to sea level and consecutively to simulated altitude (FiO2: 15.1% equivalent to 2500m above sea level) administered by an altitude Simulator (Altitrainer, SMTEC), simulated altitude (FiO2: 15.1%), with a facemask. \| Device: Simulated Altitude (FiO2: 15.1%)<br>* Inhalation of deoxygenated air through a altitude simulator (Altitrainer), for approx. 1 hour. given by a facemask.<br>Device: Shamed Hypoxia (FiO2: 20.9)<br>* Inhalation of unmodified air through an altitude simulator (Altitrainer) for approximately 1 hour given by a facemask<br>\| \| Experimental: Order hypoxia-air<br>The participant will be exposed to hypoxia (FiO2, 15.1% equivalent to 2500m above sea level), simulated altitude (FiO2: 15.1%), and consecutively to shamed hypoxia (FiO2, 20.9%) administered by an altitude simulator (Altitrainer, SMTEC) with a facemask. \| Device: Simulated Altitude (FiO2: 15.1%)<br>* Inhalation of deoxygenated air through a altitude simulator (Altitrainer), for approx. 1 hour. given by a facemask.<br>Device: Shamed Hypoxia (FiO2: 20.9)<br>* Inhalation of unmodified air through an altitude simulator (Altitrainer) for approximately 1 hour given by a facemask<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Echocardiographic assessment under hypoxia (FiO2: 15.1) \| Pulmonary artery pressure measured by echo (TTE) \| 2 hours \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Echocardiographic assessment of the right heart under hypoxia (FiO2: 15.1) \| Right heart functions measured by echo (TTE) (fac, d-shaping, kinetic etc.) \| 2 hours \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Simulated altitude, Pulmonary artery pressure, Echocardiography, Right heart function
NCT02688153	EDWARDS INTUITY Valve System CADENCE Study	The study purpose is to compare the EDWARDS INTUITY valve system with commercially available stented aortic bioprostheses, in patients requiring aortic valve replacement surgery with coronary artery bypass.	This is a randomized study comparing the cross-clamp time (XCT) and cardiopulmonary bypass time (CPBT) of the EDWARDS INTUITY valve system with any commercially available stented aortic bioprosthesis, in patients with logistic EuroSCORE 1 ≥ 6 undergoing elective surgical aortic valve replacement surgery with concomitant coronary bypass grafts.~Additionally, the aim is to gather sufficient data to quantify the effect size of short term patient benefit outcomes previously identified from literature and finally to explore additional healthcare resource utilization or health economic endpoints.	A Randomized Comparison of the EDWARDS INTUITY Valve System anD commErcially Available Aortic Bioprostheses in Subjects uNdergoing surgiCal Aortic Valve replacEment	Aortic Valve Disease, Aortic Stenosis	* Device: EDWARDS INTUITY * Device: Stented aortic bioprostheses	Inclusion:~≥18 years of age~aortic stenosis / mixed aortic stenosis and aortic insufficiency~SAVR+CABG (1-4 distal anastomoses)~Log. EuroSCORE ≥6~NYHA Class ≥II~Exclusion (i.a.):~pure aortic insufficiency~pre-existing prosthetic heart valve or ring~congenital true bicuspid / unicuspid aortic valve~LVEF <20%	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Average Subject Time Spent on Cardiopulmonary Cross Clamp \| Cardiopulmonary cross clamp time is the amount of time that the patient's aorta (blood vessel) is clamped by a surgical instrument used in cardiac surgery. This allows the normal blood flow to be sent to an artificial heart and lung machine to keep it at a constant temperature and oxygen level. \| At time of surgery, an average of 1.5 hours \| \| Average Amount of Time Subject Spent on Cardiopulmonary Bypass \| Cardiopulmonary bypass time is the amount of time that the patient's blood circulates through an artificial heart and lung machine during cardiac surgery. \| At time of surgery, an average of 2 hours \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at 2 Years. \| The New York Heart Association (NYHA) functional classification system relates symptoms to everyday activities and the patient's quality of life. Class I. Patients with cardiac disease but without resulting limitation of physical activity.~Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest.~Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest.~Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.~Symptoms of heart failure or the anginal syndrome may be present even at rest. \| Baseline and 2 Years \| \| Subject's Average Mean Gradients (mmHg) Measurements Over Time. \| Mean gradient is the average flow of blood through the aortic valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. Mean gradient values depend on the size and type of valve. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subject's Average Peak Gradients (mmHg) Measurements Over Time. \| Peak gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Subject's Effective Orifice Area (EOA) Measurement Over Time. \| Effective orifice area represents the cross-sectional area of the blood flow downstream of the aortic valve. Effective orifice area is evaluated by echocardiography over time. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Subject's Effective Orifice Area Index (EOAI) Measurement Over Time. \| Effective orifice area index represents the minimal cross-sectional area of the blood flow downstream of the aortic valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Amount of Aortic Valvular Regurgitation Over Time. \| Aortic valvular regurgitation occurs when the aortic valve in the heart does not close tightly allowing some of the blood that was pumped out of the heart to leak back into it. Aortic valvular regurgitation is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 represents no regurgitation and 4 represents severe regurgitation. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Conversion of Edwards INTUITY Surgical Aortic Valve to Control During Surgery. \| Subjects randomized to the Edwards INTUITY group that were converted to the control group and received commercially available surgical aortic heart valves during surgery. \| Prior to Surgery \| \| Subjects Who Required a Thoracic Resternotomy Over Time \| Number of Subjects who had a surgical opening of their chest after their initial aortic heart valve surgery shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Received a Permanent Pacemaker Over Time. \| Number of Subjects who received a Permanent Pacemaker shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Major Paravalvular Leak (OPC) Over Time \| Number of subjects who experienced a Major Paravalvular Leak (OPC) shown over various time points.~Paravalvular leak refers to blood flowing through a channel between the implanted artificial valve and the cardiac tissue as a result of inappropriate sealing.~Paravalvular leak is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. A major paravalvular leak (OPC)are any events of leak that required surgical intervention or were considered an serious adverse event. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Experienced Major Bleeding Over Time. \| Number of subjects who experienced Major Bleeding shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Experienced Respiratory Failure Over Time \| Number of subjects who experienced a Respiratory Failure shown over various time points. Respiratory failure happens when not enough oxygen passes from your lungs to your blood. \| 30 days, 3 Months , 6 Months, 1 Year, 2 Years. \| \| Subjects With a Cerebral Vascular Accident or Permanent Stroke Over Time \| Number of subjects who experienced a Cerebral Vascular Accident or Permanent Stroke shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With Renal Failure Over Time \| Number of subjects who experienced Renal (kidney) Failure shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With Endocarditis Over Time \| Number of subjects who experienced Endocarditis shown over various time points. Endocarditis is an infection of the endocardium, which is the inner lining of your heart chambers and heart valves. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Deep Sternal Would Infection Over Time \| Number of subjects who experienced a Deep Sternal Wound Infection shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Myocardial Infarction Over Time \| Number of subjects who experienced a Myocardial Infarction shown over various time points. A Myocardial infarction, commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Thromboembolism Over Time \| Number of subjects who experienced a Thromboembolism shown over various time points. A thromboembolism is an obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Cardiac Tamponade Over Time \| Number of subjects who experienced a Cardiac Tamponade shown over various time points. Cardiac tamponade is when fluid in the pericardium (the sac around the heart) builds up and results in compression (squeezing) of the heart. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Cardiac Reoperation for Any Reason Over Time \| Number of subjects who experienced a Cardiac reoperation for any reason shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Died Intraoperatively \| Number of subjects who died during surgery. \| Surgery \| \| Subject's Average Score on the EQ-5D- Quality of Life Questionnaire Over Time \| The EQ-5D is a standardized questionnaire that asks subjects to rate themselves (no problems, some problems, extreme problems) on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scale is indexed and ranges from a minimum of 0.275 and a maximum of 1.000. A lower number indicates the participants experiences more problems and a higher number indicates the participants experiences fewer problems. \| Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subject's Average Score SF-12 - Quality of Life Questionnaire Over Time \| The Medical Outcomes Study Short-Form 12 (SF-12) - Physical Component Summary (PCS) and Mental Component Summary (MCS).~The SF-12 questionnaire scale ranges from 100, which reflects the best health status to 0, which reflects the worse health status.~Subject's Average Score at Baseline and at each follow-up interval until 2 year - SF-12. \| Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subject's Average Score on the KCCQ - Quality of Life Questionnaire Over Time \| The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores range from 0-100, in which higher scores reflect better health status. Subjects took this questionnaire at baseline, 30 days, 3 Months, 6 Months, 1 Year, and 2 Years. \| Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Health Care Utilization \| The average amount of time the subjects spent in the intensive care unit, the intermediate care length of stay, and the average total length of hospital stay after their heart valve replacement procedure. \| Day of surgical procedure through discharge from the hospital, an average of 2 weeks \|	Aortic Valve Replacement, Aortic Stenosis, EDWARDS INTUITY	Aortic Valve Stenosis, Aortic Valve Disease, Heart Valve Diseases, Heart Diseases, Cardiovascular Diseases, Ventricular Outflow Obstruction	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: EDWARDS INTUITY<br>EDWARDS INTUITY Valve System, Model 8300A \| Device: EDWARDS INTUITY<br>* To evaluate cardiac performance characteristics and adverse events rates associated with the EDWARDS INTUITY Valve in patients undergoing AVR & CABG.<br>* Other names: aortic valve replacement;\| \| Active Comparator: Stented aortic bioprostheses<br>Stented aortic bioprostheses \| Device: Stented aortic bioprostheses<br>* In comparison to control valves available on the market.<br>* Other names: aortic valve replacement;\|	EDWARDS INTUITY Valve System CADENCE Study Study Overview ================= Brief Summary ----------------- The study purpose is to compare the EDWARDS INTUITY valve system with commercially available stented aortic bioprostheses, in patients requiring aortic valve replacement surgery with coronary artery bypass. Detailed Description ----------------- This is a randomized study comparing the cross-clamp time (XCT) and cardiopulmonary bypass time (CPBT) of the EDWARDS INTUITY valve system with any commercially available stented aortic bioprosthesis, in patients with logistic EuroSCORE 1 ≥ 6 undergoing elective surgical aortic valve replacement surgery with concomitant coronary bypass grafts. Additionally, the aim is to gather sufficient data to quantify the effect size of short term patient benefit outcomes previously identified from literature and finally to explore additional healthcare resource utilization or health economic endpoints. Official Title ----------------- A Randomized Comparison of the EDWARDS INTUITY Valve System anD commErcially Available Aortic Bioprostheses in Subjects uNdergoing surgiCal Aortic Valve replacEment Conditions ----------------- Aortic Valve Disease, Aortic Stenosis Intervention / Treatment ----------------- * Device: EDWARDS INTUITY * Device: Stented aortic bioprostheses Participation Criteria ================= Eligibility Criteria ----------------- Inclusion: ≥18 years of age aortic stenosis / mixed aortic stenosis and aortic insufficiency SAVR+CABG (1-4 distal anastomoses) Log. EuroSCORE ≥6 NYHA Class ≥II Exclusion (i.a.): pure aortic insufficiency pre-existing prosthetic heart valve or ring congenital true bicuspid / unicuspid aortic valve LVEF <20% Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: EDWARDS INTUITY<br>EDWARDS INTUITY Valve System, Model 8300A \| Device: EDWARDS INTUITY<br>* To evaluate cardiac performance characteristics and adverse events rates associated with the EDWARDS INTUITY Valve in patients undergoing AVR & CABG.<br>* Other names: aortic valve replacement;\| \| Active Comparator: Stented aortic bioprostheses<br>Stented aortic bioprostheses \| Device: Stented aortic bioprostheses<br>* In comparison to control valves available on the market.<br>* Other names: aortic valve replacement;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Average Subject Time Spent on Cardiopulmonary Cross Clamp \| Cardiopulmonary cross clamp time is the amount of time that the patient's aorta (blood vessel) is clamped by a surgical instrument used in cardiac surgery. This allows the normal blood flow to be sent to an artificial heart and lung machine to keep it at a constant temperature and oxygen level. \| At time of surgery, an average of 1.5 hours \| \| Average Amount of Time Subject Spent on Cardiopulmonary Bypass \| Cardiopulmonary bypass time is the amount of time that the patient's blood circulates through an artificial heart and lung machine during cardiac surgery. \| At time of surgery, an average of 2 hours \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at 2 Years. \| The New York Heart Association (NYHA) functional classification system relates symptoms to everyday activities and the patient's quality of life. Class I. Patients with cardiac disease but without resulting limitation of physical activity. Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. \| Baseline and 2 Years \| \| Subject's Average Mean Gradients (mmHg) Measurements Over Time. \| Mean gradient is the average flow of blood through the aortic valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. Mean gradient values depend on the size and type of valve. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subject's Average Peak Gradients (mmHg) Measurements Over Time. \| Peak gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Subject's Effective Orifice Area (EOA) Measurement Over Time. \| Effective orifice area represents the cross-sectional area of the blood flow downstream of the aortic valve. Effective orifice area is evaluated by echocardiography over time. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Subject's Effective Orifice Area Index (EOAI) Measurement Over Time. \| Effective orifice area index represents the minimal cross-sectional area of the blood flow downstream of the aortic valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Amount of Aortic Valvular Regurgitation Over Time. \| Aortic valvular regurgitation occurs when the aortic valve in the heart does not close tightly allowing some of the blood that was pumped out of the heart to leak back into it. Aortic valvular regurgitation is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 represents no regurgitation and 4 represents severe regurgitation. \| 30 days, 3 months, 6 months, 1 year, 2 year \| \| Conversion of Edwards INTUITY Surgical Aortic Valve to Control During Surgery. \| Subjects randomized to the Edwards INTUITY group that were converted to the control group and received commercially available surgical aortic heart valves during surgery. \| Prior to Surgery \| \| Subjects Who Required a Thoracic Resternotomy Over Time \| Number of Subjects who had a surgical opening of their chest after their initial aortic heart valve surgery shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Received a Permanent Pacemaker Over Time. \| Number of Subjects who received a Permanent Pacemaker shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Major Paravalvular Leak (OPC) Over Time \| Number of subjects who experienced a Major Paravalvular Leak (OPC) shown over various time points. Paravalvular leak refers to blood flowing through a channel between the implanted artificial valve and the cardiac tissue as a result of inappropriate sealing. Paravalvular leak is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. A major paravalvular leak (OPC)are any events of leak that required surgical intervention or were considered an serious adverse event. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Experienced Major Bleeding Over Time. \| Number of subjects who experienced Major Bleeding shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Experienced Respiratory Failure Over Time \| Number of subjects who experienced a Respiratory Failure shown over various time points. Respiratory failure happens when not enough oxygen passes from your lungs to your blood. \| 30 days, 3 Months , 6 Months, 1 Year, 2 Years. \| \| Subjects With a Cerebral Vascular Accident or Permanent Stroke Over Time \| Number of subjects who experienced a Cerebral Vascular Accident or Permanent Stroke shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With Renal Failure Over Time \| Number of subjects who experienced Renal (kidney) Failure shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With Endocarditis Over Time \| Number of subjects who experienced Endocarditis shown over various time points. Endocarditis is an infection of the endocardium, which is the inner lining of your heart chambers and heart valves. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Deep Sternal Would Infection Over Time \| Number of subjects who experienced a Deep Sternal Wound Infection shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Myocardial Infarction Over Time \| Number of subjects who experienced a Myocardial Infarction shown over various time points. A Myocardial infarction, commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Thromboembolism Over Time \| Number of subjects who experienced a Thromboembolism shown over various time points. A thromboembolism is an obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Cardiac Tamponade Over Time \| Number of subjects who experienced a Cardiac Tamponade shown over various time points. Cardiac tamponade is when fluid in the pericardium (the sac around the heart) builds up and results in compression (squeezing) of the heart. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects With a Cardiac Reoperation for Any Reason Over Time \| Number of subjects who experienced a Cardiac reoperation for any reason shown over various time points. \| 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subjects Who Died Intraoperatively \| Number of subjects who died during surgery. \| Surgery \| \| Subject's Average Score on the EQ-5D- Quality of Life Questionnaire Over Time \| The EQ-5D is a standardized questionnaire that asks subjects to rate themselves (no problems, some problems, extreme problems) on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scale is indexed and ranges from a minimum of 0.275 and a maximum of 1.000. A lower number indicates the participants experiences more problems and a higher number indicates the participants experiences fewer problems. \| Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subject's Average Score SF-12 - Quality of Life Questionnaire Over Time \| The Medical Outcomes Study Short-Form 12 (SF-12) - Physical Component Summary (PCS) and Mental Component Summary (MCS). The SF-12 questionnaire scale ranges from 100, which reflects the best health status to 0, which reflects the worse health status. Subject's Average Score at Baseline and at each follow-up interval until 2 year - SF-12. \| Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Subject's Average Score on the KCCQ - Quality of Life Questionnaire Over Time \| The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores range from 0-100, in which higher scores reflect better health status. Subjects took this questionnaire at baseline, 30 days, 3 Months, 6 Months, 1 Year, and 2 Years. \| Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. \| \| Health Care Utilization \| The average amount of time the subjects spent in the intensive care unit, the intermediate care length of stay, and the average total length of hospital stay after their heart valve replacement procedure. \| Day of surgical procedure through discharge from the hospital, an average of 2 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Aortic Valve Replacement, Aortic Stenosis, EDWARDS INTUITY
NCT00575003	Study to Investigate an Immunomodulatory Therapy in Adult Patients With Perennial Allergic Rhinoconjunctivitis	The purpose of the study is to test the efficacy of a vaccine against house dust mite and/or cat allergy compared to placebo in adult patients.		Double-Blind, Placebo-Controlled Study to Investigate an Immunomodulatory Therapy (CYT003-QbG10) in Adult Patients With Perennial Allergic Rhinoconjunctivitis	Perennial Allergy to House Dust Mite and/or Cat	* Drug: CYT003-QbG10	Inclusion Criteria:~Mild to moderate perennial allergic rhinoconjunctivitis due to hypersensitization towards house dust mite and/or cat allergens~Exclusion Criteria:~Clinical relevant other allergies (perennial or seasonal) that could potentially interfere with the patient's study treatment schedule or assessments.~Use of any concomitant medication that could affect the patient's study treatment response or assessment results.~Any clinically relevant concomitant disease as judged by the investigator.~Pregnancy or female planning to become pregnant during the study.	18 Years	65 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Conjunctival provocation test with allergen and rhinoconjunctivitis symptoms in daily life \| \| on 4 occations over 1 year \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Safety and tolerability of the vaccine by collection of adverse events \| \| at each visit \|		Dust Mite Allergy, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases, Rhinitis, Allergic, Perennial, Rhinitis, Allergic, Rhinitis, Nose Diseases, Respiratory Tract Diseases, Respiratory Hypersensitivity, Otorhinolaryngologic Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: 1<br> \| Drug: CYT003-QbG10<br>* 6 subcutaneous injections<br>\| \| Placebo Comparator: 2<br> \| Drug: CYT003-QbG10<br>* 6 subcutaneous injections<br>\|	Study to Investigate an Immunomodulatory Therapy in Adult Patients With Perennial Allergic Rhinoconjunctivitis Study Overview ================= Brief Summary ----------------- The purpose of the study is to test the efficacy of a vaccine against house dust mite and/or cat allergy compared to placebo in adult patients. Official Title ----------------- Double-Blind, Placebo-Controlled Study to Investigate an Immunomodulatory Therapy (CYT003-QbG10) in Adult Patients With Perennial Allergic Rhinoconjunctivitis Conditions ----------------- Perennial Allergy to House Dust Mite and/or Cat Intervention / Treatment ----------------- * Drug: CYT003-QbG10 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Mild to moderate perennial allergic rhinoconjunctivitis due to hypersensitization towards house dust mite and/or cat allergens Exclusion Criteria: Clinical relevant other allergies (perennial or seasonal) that could potentially interfere with the patient's study treatment schedule or assessments. Use of any concomitant medication that could affect the patient's study treatment response or assessment results. Any clinically relevant concomitant disease as judged by the investigator. Pregnancy or female planning to become pregnant during the study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: 1<br> \| Drug: CYT003-QbG10<br>* 6 subcutaneous injections<br>\| \| Placebo Comparator: 2<br> \| Drug: CYT003-QbG10<br>* 6 subcutaneous injections<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Conjunctival provocation test with allergen and rhinoconjunctivitis symptoms in daily life \| \| on 4 occations over 1 year \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Safety and tolerability of the vaccine by collection of adverse events \| \| at each visit \|
NCT04056728	A Phase IV Study to Assess the Safety of EupentaTM Inj	A prospective, open-label, interventional phase IV study to assess the safety of EupentaTM Inj.{fully liquid pentavalent vaccine, Adsorbed Diphtheria-Tetanus-whole-cell Pertussis-Hepatitis B (rDNA [recombinant-deoxyribonucleic acid])-Haemophilus influenzae type b conjugate vaccine}		A Prospective, Open-label, Interventional Phase IV Study to Assess the Safety of EupentaTM Inj. {Fully Liquid Pentavalent Vaccine, Adsorbed Diphtheria-Tetanus-whole-cell Pertussis-Hepatitis B (rDNA [Recombinant-deoxyribonucleic Acid])-Haemophilus Influenzae Type b Conjugate Vaccine}	Hepatitis B, Diphtheria, Haemophilus Influenzae Type B Infection, Tetanus, Pertussis	* Biological: Eupenta Inj.	Inclusion Criteria:~Written informed consent obtained from the parents or legally acceptable representatives (LARs) of the subject who have been informed of the purpose, method, effects, etc., of the study~A male or female 6 to 8 weeks of age, inclusive, at the time of the first vaccination~In good health as determined by medical history, physical examination, and judgment by the Investigator~Body weight 3.2 kg and over at the time of screening~Subjects for whom the Investigator believed that their parent(s)/LAR(s) could comply with the requirements of the protocol (e.g., completion of the Subject Diary Cards, return for site visits)~Exclusion Criteria:~Past or present medical history of known or suspected diphtheria, tetanus, pertussis, polio, HB and/or Hib diseases~Any history of allergy to any of the components or excipients of EupentaTM Inj., including aluminum hydroxide, sodium hydrogen phosphate heptahydrate, monobasic sodium phosphate dihydrate, polysorbate and thimerosal~Any medical condition which can compromise the infant's safety, as per Investigator's discretion~History of seizures or abnormal cerebral signs in the newborn period or other serious neurological abnormality~History of bleeding tendencies~Household contact and/or intimate exposure with a confirmed case of diphtheria, pertussis, HB, polio and/or Hib diseases within in 30 days prior to screening~History of fever ≥ 38°C/ 100.4°F within 3 days prior to screening and/or intake of anti-pyretic/analgesic medication. Subjects who meet this criterion will be rescreened to check the temperature after the temporary condition has resolved and if they are within the window period for age of first vaccination at the time of re-scheduled visit~History of previous diphtheria-tetanus-pertussis (DTP), and/or Hib vaccination doses~History of previous or concurrent vaccinations other than Bacillus Calmette-Guérin (BCG), HB vaccination at birth, Polio, Rotavirus and Pneumococcal vaccines~Known or suspected immune disorders, or, received immunosuppressive therapy~Participation 30 days prior to screening in the study or simultaneously in another study and/or received any investigational product	6 Weeks	8 Weeks	All	Accepts Healthy Volunteers	Primary Purpose: Prevention Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of any immediate reactions reported from the study after EupentaTM Inj. Vaccination \| \| first 30 minutes after each study vaccination \| \| Incidence of solicited local and systemic adverse events (AEs) \| \| baseline(pre-vaccination) up to 7 days after each vaccination \| \| Incidence of any unsolicited AEs during the entire study \| \| through study completion, an average of 1 year \| \| Incidence of SAEs during the entire study period \| \| through study completion, an average of 1 year \|			Blood-Borne Infections, Hepatitis, Liver Diseases, Influenza, Human, Hepatitis B, Whooping Cough, Tetanus, Diphtheria, Haemophilus Infections, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Infections, RNA Virus Infections, Respiratory Tract Infections, Orthomyxoviridae Infections, Respiratory Tract Diseases, Communicable Diseases, Hepadnaviridae Infections, DNA Virus Infections, Bordetella Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Bacterial Infections and Mycoses, Clostridium Infections, Gram-Positive Bacterial Infections, Corynebacterium Infections, Actinomycetales Infections, Pasteurellaceae Infections	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Eupenta Inj.<br> \| Biological: Eupenta Inj.<br>* fully liquid pentavalent vaccine, Adsorbed Diphtheria-Tetanus-whole-cell Pertussis-Hepatitis B (rDNA [recombinant-deoxyribonucleic acid])-Haemophilus influenzae type b conjugate vaccine single dose 0.5 mL/vial The vaccine is given at 6, 10 and 14 weeks of age in infants.<br>\|	A Phase IV Study to Assess the Safety of EupentaTM Inj Study Overview ================= Brief Summary ----------------- A prospective, open-label, interventional phase IV study to assess the safety of EupentaTM Inj.{fully liquid pentavalent vaccine, Adsorbed Diphtheria-Tetanus-whole-cell Pertussis-Hepatitis B (rDNA [recombinant-deoxyribonucleic acid])-Haemophilus influenzae type b conjugate vaccine} Official Title ----------------- A Prospective, Open-label, Interventional Phase IV Study to Assess the Safety of EupentaTM Inj. {Fully Liquid Pentavalent Vaccine, Adsorbed Diphtheria-Tetanus-whole-cell Pertussis-Hepatitis B (rDNA [Recombinant-deoxyribonucleic Acid])-Haemophilus Influenzae Type b Conjugate Vaccine} Conditions ----------------- Hepatitis B, Diphtheria, Haemophilus Influenzae Type B Infection, Tetanus, Pertussis Intervention / Treatment ----------------- * Biological: Eupenta Inj. Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Written informed consent obtained from the parents or legally acceptable representatives (LARs) of the subject who have been informed of the purpose, method, effects, etc., of the study A male or female 6 to 8 weeks of age, inclusive, at the time of the first vaccination In good health as determined by medical history, physical examination, and judgment by the Investigator Body weight 3.2 kg and over at the time of screening Subjects for whom the Investigator believed that their parent(s)/LAR(s) could comply with the requirements of the protocol (e.g., completion of the Subject Diary Cards, return for site visits) Exclusion Criteria: Past or present medical history of known or suspected diphtheria, tetanus, pertussis, polio, HB and/or Hib diseases Any history of allergy to any of the components or excipients of EupentaTM Inj., including aluminum hydroxide, sodium hydrogen phosphate heptahydrate, monobasic sodium phosphate dihydrate, polysorbate and thimerosal Any medical condition which can compromise the infant's safety, as per Investigator's discretion History of seizures or abnormal cerebral signs in the newborn period or other serious neurological abnormality History of bleeding tendencies Household contact and/or intimate exposure with a confirmed case of diphtheria, pertussis, HB, polio and/or Hib diseases within in 30 days prior to screening History of fever ≥ 38°C/ 100.4°F within 3 days prior to screening and/or intake of anti-pyretic/analgesic medication. Subjects who meet this criterion will be rescreened to check the temperature after the temporary condition has resolved and if they are within the window period for age of first vaccination at the time of re-scheduled visit History of previous diphtheria-tetanus-pertussis (DTP), and/or Hib vaccination doses History of previous or concurrent vaccinations other than Bacillus Calmette-Guérin (BCG), HB vaccination at birth, Polio, Rotavirus and Pneumococcal vaccines Known or suspected immune disorders, or, received immunosuppressive therapy Participation 30 days prior to screening in the study or simultaneously in another study and/or received any investigational product Ages Eligible for Study ----------------- Minimum Age: 6 Weeks Maximum Age: 8 Weeks Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Eupenta Inj.<br> \| Biological: Eupenta Inj.<br>* fully liquid pentavalent vaccine, Adsorbed Diphtheria-Tetanus-whole-cell Pertussis-Hepatitis B (rDNA [recombinant-deoxyribonucleic acid])-Haemophilus influenzae type b conjugate vaccine single dose 0.5 mL/vial The vaccine is given at 6, 10 and 14 weeks of age in infants.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of any immediate reactions reported from the study after EupentaTM Inj. Vaccination \| \| first 30 minutes after each study vaccination \| \| Incidence of solicited local and systemic adverse events (AEs) \| \| baseline(pre-vaccination) up to 7 days after each vaccination \| \| Incidence of any unsolicited AEs during the entire study \| \| through study completion, an average of 1 year \| \| Incidence of SAEs during the entire study period \| \| through study completion, an average of 1 year \|
NCT01994811	Eastern Caribbean Health Outcomes Research Network (ECHORN)	The Eastern Caribbean Health Outcomes Research Network (ECHORN) is a collaborative research study that examines the lifestyles, eating habits, and health behaviors associated with cancer, diabetes and heart disease in adult men and women living in the Eastern Caribbean.	The Eastern Caribbean Health Outcomes Research Network (ECHORN) has two aims: (1) To form a research collaborative across the Eastern Caribbean islands of Puerto Rico, the U.S. Virgin Islands, Barbados, and Trinidad & Tobago to recruit and follow a community-dwelling adult cohort to estimate the prevalence of known and potential risk factors associated with the development of heart disease, cancer, and diabetes and (2) To enhance health outcomes research leadership capacity in the region through a series of dedicated activities locally and abroad. ECHORN will expand clinical research with racial/ethnic minority populations in a transitioning part of the globe now threatened with an epidemic of noncommunicable chronic diseases (NCD). ECHORN's findings will have direct implications for the health disparities research and policy agenda in the mainland United States. In the long term, the links ECHORN will facilitate with local health policy delegations and global strategic organizational partners will promote the translation of research to improve health outcomes across the region. The collection and storage of biological specimens will also contribute to national biomonitoring projects and has the potential to identify unique risk and protective factors in the development of NCD.	Eastern Caribbean Health Outcomes Research Network (ECHORN)	Cancer, Cardiovascular Disease, Diabetes		Inclusion Criteria:~Greater than or equal to 40 years of age~English or Spanish language speaking~Resident of island at least 10 years~Able to provide informed consent~Non-institutionalized at the time of data collection~Stable contact/residential information~No plans to relocate from island within the next 5 years	40 Years	null	All	Accepts Healthy Volunteers		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Prevalence of non-communicable diseases \| Prevalence of non-communicable diseases, including cancer, heart disease and diabetes. \| 5 years \|		cancer, cardiovascular disease, diabetes	Cardiovascular Diseases		Eastern Caribbean Health Outcomes Research Network (ECHORN) Study Overview ================= Brief Summary ----------------- The Eastern Caribbean Health Outcomes Research Network (ECHORN) is a collaborative research study that examines the lifestyles, eating habits, and health behaviors associated with cancer, diabetes and heart disease in adult men and women living in the Eastern Caribbean. Detailed Description ----------------- The Eastern Caribbean Health Outcomes Research Network (ECHORN) has two aims: (1) To form a research collaborative across the Eastern Caribbean islands of Puerto Rico, the U.S. Virgin Islands, Barbados, and Trinidad & Tobago to recruit and follow a community-dwelling adult cohort to estimate the prevalence of known and potential risk factors associated with the development of heart disease, cancer, and diabetes and (2) To enhance health outcomes research leadership capacity in the region through a series of dedicated activities locally and abroad. ECHORN will expand clinical research with racial/ethnic minority populations in a transitioning part of the globe now threatened with an epidemic of noncommunicable chronic diseases (NCD). ECHORN's findings will have direct implications for the health disparities research and policy agenda in the mainland United States. In the long term, the links ECHORN will facilitate with local health policy delegations and global strategic organizational partners will promote the translation of research to improve health outcomes across the region. The collection and storage of biological specimens will also contribute to national biomonitoring projects and has the potential to identify unique risk and protective factors in the development of NCD. Official Title ----------------- Eastern Caribbean Health Outcomes Research Network (ECHORN) Conditions ----------------- Cancer, Cardiovascular Disease, Diabetes Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Greater than or equal to 40 years of age English or Spanish language speaking Resident of island at least 10 years Able to provide informed consent Non-institutionalized at the time of data collection Stable contact/residential information No plans to relocate from island within the next 5 years Ages Eligible for Study ----------------- Minimum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Prevalence of non-communicable diseases \| Prevalence of non-communicable diseases, including cancer, heart disease and diabetes. \| 5 years \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- cancer, cardiovascular disease, diabetes
NCT04545879	Investigating the Gut Microbiota Modulation Effects of Allicin for Cardiovascular Disease Protection and Establishing Microbiota Directed Personalized Nutrition Guidance With Novel Humanized Gnotobiotic Mice Model, Microbial Culturomics and Metabolomic Technique	Investigators recruited 10 trimethylamine N-oxide (TMAO) producers to test the effect of garlic juice containing allicin on gut microbiota modulation and TMAO production.	Trimethylamine N-oxide (TMAO) was recently discovered as a novel and independent risk factor for promoting atherosclerosis while it is generated from dietary carnitine through the metabolism of gut microbiota for decades. Allicin, the major compound in raw garlic juice, is a naturally antimicrobial phytochemical found in raw garlic juice and easily acquired from the diet. Investigators' previous study suggests dietary allicin reduces the transformation of L-carnitine to TMAO through the impact on gut microbiota in mice. Therefore, it is worth investigating whether raw garlic juice intake could reduce the TMAO productivity of human gut microbiota as well as modulate gut microflora. Investigators plan to recruit 10 TMAO producers to receive garlic juice for one week. The plasma and urine TMAO concentration will be measured by the LC-MS, and the gut microbiota composition will be analyzed by the next-generation sequencing, through bioinformatics analysis. Investigators expected after intake garlic juice for one week, it could prevent the cardiovascular disease risk via gut microbiota modulation and reduction of plasma and urine TMAO.~Screening of the TMAO producer:~The healthy participants were recruited, the criteria as follows: (1) age ≥ 20 years old; (2) no exposure to antibiotics, probiotics, or carnitine supplements within the previous month; (3) have no history of chronic diseases including, diabetes mellitus, myasthenia gravis, chronic renal disease, hyperparathyroidism, epilepsy, and severe anemia; (4) Participants were excluded from the study if they reported recent gastrointestinal discomfort (such as abdominal pain or diarrhea). To screening the TMAO producer, Investigators use the oral carnitine challenge test (OCCT) method which previously exhibited better efficacy than fasting plasma TMAO to identify the TMAO producer phenotype. All of the participants fasted at least 8 hours before performing OCCT. 1500 mg of L-carnitine (3 tablets, General Nutrition Centers, Inc., USA) orally administrated to the participants. The blood and urine of participants were collected at 0, 24, 48, and 72 hours after carnitine intake. Participants with plasma TMAO ≧ 10 μM after OCCT were defined as high TMAO producers and proceeded into the garlic juice intervention test.~Garlic Juice Intervention:~High-TMAO producers asked to consume 55 mL of raw garlic juice (48 mg of allicin equivalent) once a day during dinner for one week. High-TMAO producers suggested consuming the garlic juice with a meal. The high-TMAO producers were free to choose their diet, no restriction on the type of food. After one week of raw garlic juice intervention, the second OCCT was performed.	Investigating the Gut Microbiota Modulation Effects of Allicin for Cardiovascular Disease Protection and Establishing Microbiota Directed Personalized Nutrition Guidance With Novel Humanized Gnotobiotic Mice Model, Microbial Culturomics and Metabolomic Technique	Atherosclerosis	* Dietary Supplement: Raw garlic juice containing allicin	Inclusion Criteria:~Age 20-65 years old~Healthy subjects with TMAO producing ability~Exclusion Criteria:~Exposure to antibiotics, probiotics, or carnitine supplements within the previous month~Have a history of chronic diseases including, diabetes mellitus, myasthenia gravis, chronic renal disease, hyperparathyroidism, epilepsy, and severe anemia~Have gastrointestinal discomfort (such as abdominal pain or diarrhea)	20 Years	65 Years	All	Accepts Healthy Volunteers	Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Plasma and urine TMAO level (ppm) \| Quantitation of plasma and urine TMAO level by LC-MS \| 6 months \| \| Compositional analysis of gut microbiota (% of different bacteria species) \| Next-generation sequencing and bioinformatics \| 6 months \|			Antioxidants, Allicin, Anti-Infective Agents, Hypolipidemic Agents, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Lipid Regulating Agents, Protective Agents, Physiological Effects of Drugs, Hypoglycemic Agents, Free Radical Scavengers	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Raw garlic juice<br>Raw garlic juice treatment group \| Dietary Supplement: Raw garlic juice containing allicin<br>* Fresh garlic juice containing around 48mg allicin for 7 days<br>\|	Investigating the Gut Microbiota Modulation Effects of Allicin for Cardiovascular Disease Protection and Establishing Microbiota Directed Personalized Nutrition Guidance With Novel Humanized Gnotobiotic Mice Model, Microbial Culturomics and Metabolomic Technique Study Overview ================= Brief Summary ----------------- Investigators recruited 10 trimethylamine N-oxide (TMAO) producers to test the effect of garlic juice containing allicin on gut microbiota modulation and TMAO production. Detailed Description ----------------- Trimethylamine N-oxide (TMAO) was recently discovered as a novel and independent risk factor for promoting atherosclerosis while it is generated from dietary carnitine through the metabolism of gut microbiota for decades. Allicin, the major compound in raw garlic juice, is a naturally antimicrobial phytochemical found in raw garlic juice and easily acquired from the diet. Investigators' previous study suggests dietary allicin reduces the transformation of L-carnitine to TMAO through the impact on gut microbiota in mice. Therefore, it is worth investigating whether raw garlic juice intake could reduce the TMAO productivity of human gut microbiota as well as modulate gut microflora. Investigators plan to recruit 10 TMAO producers to receive garlic juice for one week. The plasma and urine TMAO concentration will be measured by the LC-MS, and the gut microbiota composition will be analyzed by the next-generation sequencing, through bioinformatics analysis. Investigators expected after intake garlic juice for one week, it could prevent the cardiovascular disease risk via gut microbiota modulation and reduction of plasma and urine TMAO. Screening of the TMAO producer: The healthy participants were recruited, the criteria as follows: (1) age ≥ 20 years old; (2) no exposure to antibiotics, probiotics, or carnitine supplements within the previous month; (3) have no history of chronic diseases including, diabetes mellitus, myasthenia gravis, chronic renal disease, hyperparathyroidism, epilepsy, and severe anemia; (4) Participants were excluded from the study if they reported recent gastrointestinal discomfort (such as abdominal pain or diarrhea). To screening the TMAO producer, Investigators use the oral carnitine challenge test (OCCT) method which previously exhibited better efficacy than fasting plasma TMAO to identify the TMAO producer phenotype. All of the participants fasted at least 8 hours before performing OCCT. 1500 mg of L-carnitine (3 tablets, General Nutrition Centers, Inc., USA) orally administrated to the participants. The blood and urine of participants were collected at 0, 24, 48, and 72 hours after carnitine intake. Participants with plasma TMAO ≧ 10 μM after OCCT were defined as high TMAO producers and proceeded into the garlic juice intervention test. Garlic Juice Intervention: High-TMAO producers asked to consume 55 mL of raw garlic juice (48 mg of allicin equivalent) once a day during dinner for one week. High-TMAO producers suggested consuming the garlic juice with a meal. The high-TMAO producers were free to choose their diet, no restriction on the type of food. After one week of raw garlic juice intervention, the second OCCT was performed. Official Title ----------------- Investigating the Gut Microbiota Modulation Effects of Allicin for Cardiovascular Disease Protection and Establishing Microbiota Directed Personalized Nutrition Guidance With Novel Humanized Gnotobiotic Mice Model, Microbial Culturomics and Metabolomic Technique Conditions ----------------- Atherosclerosis Intervention / Treatment ----------------- * Dietary Supplement: Raw garlic juice containing allicin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 20-65 years old Healthy subjects with TMAO producing ability Exclusion Criteria: Exposure to antibiotics, probiotics, or carnitine supplements within the previous month Have a history of chronic diseases including, diabetes mellitus, myasthenia gravis, chronic renal disease, hyperparathyroidism, epilepsy, and severe anemia Have gastrointestinal discomfort (such as abdominal pain or diarrhea) Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Raw garlic juice<br>Raw garlic juice treatment group \| Dietary Supplement: Raw garlic juice containing allicin<br>* Fresh garlic juice containing around 48mg allicin for 7 days<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Plasma and urine TMAO level (ppm) \| Quantitation of plasma and urine TMAO level by LC-MS \| 6 months \| \| Compositional analysis of gut microbiota (% of different bacteria species) \| Next-generation sequencing and bioinformatics \| 6 months \|

End of preview. Expand in Dataset Viewer.

CTGOV

🤗 [Panacea Model] • 💻 [Github Repo] • 📃 [Panacea Paper]

This repo contains ctgov data used in "Panacea: A foundation model for clinical trial search, summarization, design, and recruitment".

Load the dataset

pip install -U datasets fsspec

from datasets import load_dataset
ds = load_dataset('linjc16/ctgov', split='train')

Citation

If you find our work useful, please consider citing Panacea:

@article{lin2024panacea,
  title={Panacea: A foundation model for clinical trial search, summarization, design, and recruitment},
  author={Lin, Jiacheng and Xu, Hanwen and Wang, Zifeng and Wang, Sheng and Sun, Jimeng},
  journal={arXiv preprint arXiv:2407.11007},
  year={2024}
}

Downloads last month: 17

Size of the auto-converted Parquet files (First 5GB):

2.2 GB

Number of rows (First 5GB):

372,997

Estimated number of rows:

479,019