A Phase IIb Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures

• Status: Not yet recruiting
• Trial end date: 2026-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Diego
• Collaborators: Auckland City Hospital; Middlemore Hospital, New Zealand; Rady Children's Hospital, San Diego; Sharp Mary Birch Hospital for Women & Newborns; University of Auckland, New Zealand; University of Minnesota
• Treatments: Levetiracetam; Phenobarbital

Criteria

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.

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 life;

• Subjects in whom death seems imminent;

• Seizures caused by correctable metabolic abnormality, such as hypocalcaemia, hypoglycaemia.