Head injury is the cause of approximately 5% of all epilepsy. Individuals with severe head trauma carry a 15-50% risk of developing post-traumatic epilepsy. Past attempts at preventing epilepsy by treatment with older Anti-Epileptic Drugs (AEDs) have been unsuccessful. Levetiracetam is a new generation AED with a favorable side-effect, and pharmacokinetic profile that has potent anti-epileptogenic effects in animal models of epilepsy. It may thus be useful in preventing the development of epilepsy following Traumatic Brain Injury (TBI). However, there has been no experience in administering levetiracetam rapidly to individuals with acute TBI, including comatose patients. In this pilot study, therefore, we propose to initiate the evaluation of levetiracetam in prevention of post-traumatic epilepsy by determining the safety, tolerability, pharmacokinetics, and feasibility of acute and chronic administration of levetiracetam to individuals with head injury with a high risk for developing post-traumatic epilepsy. This will be single-dose, open-label study. 60 male and female individuals aged 6 years (40 adults, 20 children) will be enrolled. All will have head injury, with a high risk for developing post-traumatic epilepsy (injury with intracranial hemorrhage or penetrating wound injury). Individuals will receive levetiracetam 55 mg/kg/day by mouth, or via orogastric tube if unable to swallow. Treatment will start within 8 hours of head injury, and will continue for six months. In addition, individuals will receive phenytoin for one week following head injury as standard clinical care. Serum pharmacokinetic profile of levetiracetam will be checked on treatment days three and twenty eight in 20 adult and 12 pediatric subjects, divided into equal groups of those who can, and those who cannot swallow during the acute phase after head injury. The primary outcome measures will be the frequency and severity of side effects of levetiracetam, and the pharmacokinetics of orogastric administration of levetiracetam to individuals with acute head injury. Secondary outcome measures will include the rate of enrollment into, and the rate of drop-out from the study. Frequency of unprovoked seizures at 2-7 days after head injury ("early seizure"), and time to occurrence of unprovoked seizures at >7 days after head injury ("late seizure"), will be monitored but will not represent outcome criteria. The results of the present study will be used to design a large study to assess efficacy of levetiracetam in the prevention of epilepsy in individuals with head injury with a high risk for developing post-traumatic epilepsy. A positive finding of such a study would be the first successful attempt at prevention of epilepsy, a lifelong debilitating illness.
NIH ExPorter
NIH ExPorter