Efficacy of Intravenous Levetiracetam in Neonatal Seizures

Phase 1

Completed

• Conditions: Neonatal Seizures
• Interventions: Drug: Intravenous phenobarbital; Drug: Intravenous levetiracetam

• Registration Number: NCT01720667
• Lead Sponsor: Richard H. Haas

Brief Summary

A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants. Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory.

Monitoring for seizure detection will be tested at five (5) US sites and one (1) international site using the internet.

Detailed Description

This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects.

Levetiracetam (LEV) has great potential as a treatment for neonatal seizures but is not approved for use in children less than 2 years of age.

This study aims to obtain essential data regarding the efficacy and safety of LEV in this vulnerable and under researched population and simultaneously to develop EEG monitoring systems that facilitate seizure detection and research.

Specific aims are:

1. To determine the efficacy of intravenous LEV in terminating neonatal seizures when given as first line therapy.

2. To obtain dose escalation data by studying the additional efficacy of a further dose in non responders.

3. To obtain additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study.

4. To obtain further safety data of LEV in neonates.

5. To prove the feasibility of centralized remote monitoring of continuous EEG monitoring in the Neonatal Intensive Care Unit (NICU) via the internet and test a promising automated neonatal seizure detection algorithm.

The study design is a phase 2b randomized blinded controlled study.

Study Timeline

• Study First Submitted: 2012-10-22
• Study First Submitted QC: 2012-10-31
• Study First Posted: 2012-11-02
• Study Start: 2013-03
• Primary Completion: 2017-10-31
• Results First Submitted: 2019-07-03
• Study Completion: 2019-07-31
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-12
• Last Update Submitted: 2019-08-12
• Results First Posted: 2019-08-21
• Last Update Posted: 2019-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

1. Newborns admitted to any of the study sites with electrographic seizures seizures.
2. Term infants gestational age >36 weeks less than 2 weeks of age.
3. Greater than 2200 grams.
4. Infants for whom parental consent to participate in the study is obtained.

Exclusion Criteria

1. Infants who are already receiving anticonvulsants
2. If serum creatinine is greater than 1.6mM
3. If seizures are due to correctable metabolic abnormalities (i.e. hypoglycaemia, hypocalcemia, hyponatremia)
4. Subjects in whom death seems imminent, as assessed by the neonatologist.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous phenobarbital	Intravenous phenobarbital	Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance
Intravenous levetiracetam	Intravenous levetiracetam	Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance

Primary Outcome Measures

Name	Time	Method
Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)	24 hours	A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.; Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.

Secondary Outcome Measures

Name	Time	Method
Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment	48 hours	A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
Number of Neonates With Seizure Termination at 1 Hour After Treatment	1 hour	A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
LEV Dose Escalation Component	24 hours	Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.
Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia	24 hours

Trial Locations

Locations (1)

University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU); 🇺🇸 San Diego, California, United States