A Phase IIb Dose Escalation Study of Levetiracetam for the Treatment of Neonatal Seizures
University of California, San Diego
Summary
The main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. This study will be an open label dose-escalation, preliminary safety and efficacy study. There will be a randomized control treatment component. Infants recognized as having neonatal seizures or as being at risk of developing seizures will be recruited and started on continuous video EEG monitoring (CEEG). Eligibility will be confirmed and consent will be obtained. In the first 2 phases of the study, neurologists will identify neonates with mild-moderate seizure burden (less than 8 minutes cumulative seizure activity per hour), appropriate for study with LEV, and exclude patients with higher seizure burden where treatment with PHB is more appropriate. Phase 3 of the dose escalation will only proceed if additional efficacy of LEV has been demonstrated in phases 1 and 2. In Phase 3 we will recruit neonates with seizures of greater severity up to 30 minute seizure burden/hour. This will make the final results of study more generalizable. If seizures are confirmed, enrolled subjects will receive 60mg/kg of LEV. Subjects whose seizures persist or recur 15 minutes after the first infusion is complete, subjects will then be randomized in the dose escalation study. Patients in the dose escalation study will be randomly assigned to receive either higher dose LEV or treatment with the control drug PHB in a 3:1 allocation ratio, stratified by site. Funding Source- FDA OOPD
Description
Aims/Hypotheses: Primary Aim: To determine the recommended maximal safe dose of LEV in the setting of neonatal seizures of mild to moderate severity. If 60mg/kg LEV does not control seizures, subjects will be randomised to receive either additional LEV or PHB. LEV dose will be escalated in 30mg/kg increments to a maximal dose of 150mg/kg total loading dose. We will use a continual reassessment method to determine the maximal safe and tolerated dose. Secondary/exploratory aims: * To study the pharmacokinetics of high dose LEV in neonates with seizures of mild to moderate severity. * To esti…
Eligibility
- Age range
- Up to 0 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * at risk for seizures or suspected to be having seizures; * all seizure aetiologies except correctable metabolic abnormalities such as hypoglycaemia and hypocalcaemia; * Term neonates (corrected gestational age between 35 and 44 weeks, postnatal age less than 28 days); * weight \> 2200g. * Parental ability to comprehend and provide written informed consent Exclusion Criteria: * Cumulative seizure burden of 8 minutes/ hour or more in phases 1 and 2, Cumulative seizure burden of 30 minutes/hour or more in phase 3; * Renal failure defined as anuria in the first 24 hours of…
Interventions
- DrugLevetiracetam Injection
Neonates will be treated with intravenous levetiracetam 60mg/kg for first line management of seizures, and if seizures persist will be randomized to receive higher dose Levetiracetam or standard of care phenobarbital
- DrugPhenobarbital Sodium Injection
Standard of care for neonatal seizures
Locations (5)
- University of California, San DiegoSan Diego, California
- University of MinnesotaMinneapolis, Minnesota
- Auckland City HospitalAuckland, Auckland
- Middlemore HospitalAuckland, Auckland
- Capital and Coast District Health Board, Te Whatu Ora, Health New ZealandWellington, Wellington Region