Efficacy of Intravenous Levetiracetam in Neonatal Seizures

NCT ID: NCT01720667

Last Updated: 2019-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2019-07-31

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.

Conditions

Neonatal Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intravenous levetiracetam

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

Group Type: EXPERIMENTAL

Intravenous levetiracetam

Intervention Type: DRUG

Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.

Intravenous phenobarbital

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

Group Type: ACTIVE_COMPARATOR

Intravenous phenobarbital

Intervention Type: DRUG

Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.

Interventions

Intravenous levetiracetam

Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.

Intervention Type: DRUG

Intravenous phenobarbital

Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.

Intervention Type: DRUG

Other Intervention Names

Keppra; phenobarbitone

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.

• Minimum Eligible Age: 15 Minutes
• Maximum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: collaborator

Rady Children's Hospital, San Diego

OTHER

Sponsor Role: collaborator

Auckland City Hospital

OTHER_GOV

Sponsor Role: collaborator

Sharp Mary Birch Hospital for Women & Newborns

OTHER

Sponsor Role: collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: collaborator

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

Richard H. Haas

OTHER

Sponsor Role: lead

Responsible Party

Richard H. Haas

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Richard H Haas, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)

San Diego, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22495532 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30289769 (View on PubMed)

Sharpe C, Yang DZ, Haas RH, Reiner GE, Lee L, Capparelli EV; NEOLEV2 Investigators. Pharmacokinetic and pharmacodynamic data from the NEOLEV1 and NEOLEV2 studies. Arch Dis Child. 2024 Sep 25;109(10):854-860. doi: 10.1136/archdischild-2022-324952.

Reference Type: DERIVED

PMID: 38902005 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

1R01FD004147-01A1

Identifier Type: FDA

Identifier Source: secondary_id

View Link

NoGA - R01 FD004147-01A1 Haas

Identifier Type: -

Identifier Source: org_study_id