This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects. Levetiracetam (LEV) has 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 data regarding the efficacy and safety of levetiracetam in this vulnerable and under researched population, and to simultaneously develop electroencephalograph (EEG) monitoring systems that facilitate seizure detection and research.
The specific aims are: 1) To determine the efficacy of intravenous in terminating neonatal seizures when given as first line therapy. 2) To obtain dose escalation data by studying the additional efficacy of an additional 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 levetiracetum in neonates. 5) To prove the feasibility of centralized remote monitoring of continuous electroencephalograph (EEG) monitoring in the neonatal intensive care unit (NICU) via the internet and to test an automated neonatal seizure detection algorithm. The proposed study design is a phase 2, randomized, blinded, controlled study. Subjects identified as being at risk of neonatal seizures will be recruited and consent will be obtained. Continuous EEG monitoring will be used to detect seizures. This project will utilize remote centralized review via the internet of continuous video EEG monitoring from 6 different neonatal units. If seizures are detected, subjects will be randomized in a 6:4 ratio to receive either levetiracetum (40mg/kg) or phenobarbital (PHB) (20mg/kg). If electrographic seizures are still apparent at end of the load or if they recur, the newborn will receive a further 20mg/kg load of levetiracetum or 10mg/kg load of phenobarbital depending on the treatment arm. The primary endpoint studied will be seizure cessation rate following treatment with levetiracetum. Clinical and laboratory safety data and pharmacokinetic data will be obtained. The functionality of the remote continuous EEG monitoring system will be assessed, and the performance of the automated seizure detector will be compared with interpretation by two experienced neonatal encephalographers.

Public Health Relevance

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.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project (R01)
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Special Emphasis Panel (ZFD1-OPD-L (S1))
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University of California San Diego
Schools of Medicine
La Jolla
United States
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