Efficacy of Intravenous Levetiracetam in Neonatal Seizures (NEOLEV2)

Richard H. Haas

Status and phase: Completed; Phase 2; Phase 1

Conditions: Neonatal Seizures

Treatments: Drug: Intravenous levetiracetam; Drug: Intravenous phenobarbital

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01720667

NoGA - R01 FD004147-01A1 Haas

1R01FD004147-01A1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 280 patients

Sex: All

Ages: 15 minutes to 14 days old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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280 participants in 2 patient groups

Intravenous levetiracetam

Experimental group

Description:

Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance

Treatment:

Drug: Intravenous levetiracetam

Intravenous phenobarbital

Active Comparator group

Description:

Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance

Treatment:

Drug: Intravenous phenobarbital