Higher dose corticosteroids in hospitalised COVID-19 patients with hypoxia but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

Background: Low-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality. On 11 May 2022, the independent Data Monitoring Committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only to this comparison due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support continues. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 25 May 2021 and 12 May 2022, 1272 COVID-19 patients with hypoxia and receiving no oxygen (1%) or simple oxygen only (99%) were randomly allocated to receive usual care plus higher dose corticosteroids versus usual care alone (of whom 87% received low dose corticosteroids during the follow-up period). Of those randomised, 745 (59%) were in Asia, 512 (40%) in the UK and 15 (1%) in Africa. 248 (19%) had diabetes mellitus. Overall, 121 (18%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio [RR] 1.56; 95% CI 1.18-2.06; p=0.0020). There was also an excess of pneumonia reported to be due to non-COVID infection (10% vs. 6%; absolute difference 3.7%; 95% CI 0.7-6.6) and an increase in hyperglycaemia requiring increased insulin dose (22% vs. 14%; absolute difference 7.4%; 95% CI 3.2-11.5). Interpretation: In patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to usual care, which included low dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation.