Clinical trial NCT01720667: Efficacy of Intravenous Levetiracetam in Neonatal Seizures
Official title: Efficacy of Intravenous Levetiracetam in Neonatal Seizures: A Phase 2 Randomized Blinded Controlled Study of the Efficacy of Intravenous Levetiracetam (LEV) as First Line Treatment for Neonatal Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neonatal Seizures
Keywords: Seizures
Neonates
Anticonvulsants
Treatment
Levetiracetam
Phenobarbital
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: University of California, San Diego
name: Rady Children's Hospital, San Diego
name: Auckland City Hospital
name: Sharp Mary Birch Hospital for Women & Newborns
name: UCSF Benioff Children's Hospital Oakland
name: Food and Drug Administration (FDA)
First posted: 2012-11-02
Enrollment: 280
Sex: ALL
Minimum age (years): 15
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)
timeFrame: 24 hours
Secondary outcomes:
measure: Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment
timeFrame: 48 hours
measure: Number of Neonates With Seizure Termination at 1 Hour After Treatment
timeFrame: 1 hour
measure: LEV Dose Escalation Component
timeFrame: 24 hours
measure: 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
timeFrame: 24 hours
Other outcomes:
measure: Pharmacokinetic Data
timeFrame: 48 hours
measure: Feasibility of Continuous Internet EEG Monitoring
timeFrame: Subject study duration
measure: Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm
timeFrame: 48 Hours
measure: Gather Safety Information on IV Levetiracetam
timeFrame: 5 days
Locations:
city: San Diego
country: United States
facility: University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)
state: California
Study officials:
affiliation: University of California, San Diego
name: Richard H Haas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.
citation: Sharpe C, Davis SL, Reiner GE, Lee LI, Gold JJ, Nespeca M, Wang SG, Joe P, Kuperman R, Gardner M, Honold J, Lane B, Knodel E, Rowe D, Battin MR, Bridge R, Goodmar J, Castro B, Rasmussen M, Arnell K, Harbert M, Haas R. Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring. J Clin Neurophysiol. 2019 Jan;36(1):9-13. doi: 10.1097/WNP.0000000000000525.