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

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

Conditions

• Neonatal Seizure
• Neonatal Encephalopathy
• Hypoxic-Ischemic Encephalopathy
• Seizure Newborn

Interventions

DRUG

Levetiracetam 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

DRUG

Phenobarbital Sodium Injection

Standard of care for neonatal seizures

Sponsors & Collaborators

• University of Minnesota

  collaborator OTHER

• Rady Children's Hospital, San Diego

  collaborator OTHER

• Auckland City Hospital

  collaborator OTHER_GOV

• University of Auckland, New Zealand

  collaborator OTHER

• Middlemore Hospital, New Zealand

  collaborator OTHER

• University of California, San Diego

  lead OTHER

Principal Investigators

• Sonya G Wang, M.D. · University of Minnesota

• Cynthia M Sharpe, M.D. · Auckland City Hospital

• Jeff J Gold, M.D. PhD · University of California, San Diego

• Richard H Haas, MBBChir · University of California, San Diego

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

1 Month

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-03-24

Primary Completion

2027-07-01

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States
• New Zealand

Study Locations