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Efficacy of Intravenous Levetiracetam in Neonatal Seizures (NEOLEV2)

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ClinicalTrials.gov Identifier: NCT01720667
Recruitment Status : Completed
First Posted : November 2, 2012
Results First Posted : August 21, 2019
Last Update Posted : August 21, 2019
Sponsor:
Collaborators:
University of California, San Diego
Rady Children's Hospital, San Diego
Auckland City Hospital
Sharp Mary Birch Hospital for Women & Newborns
UCSF Benioff Children’s Hospital Oakland
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
Richard H. Haas, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE October 22, 2012
First Posted Date  ICMJE November 2, 2012
Results First Submitted Date  ICMJE July 3, 2019
Results First Posted Date  ICMJE August 21, 2019
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE March 2013
Actual Primary Completion Date October 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2019)
Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2012)
To determine the efficacy of intravenous LEV in terminating neonatal seizures when given as first line therapy compared to phenobarbital [ Time Frame: 48 hours ]
A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures. Seizure burden will be assessed by duration and frequency of seizure events.
Change History Complete list of historical versions of study NCT01720667 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2019)
  • Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 24 hours ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2012)
  • To obtain dose escalation data by studying the additional efficacy of a further dose in non responders. [ Time Frame: 48 hours ]
    Determine the efficacy of higher dose levetiracetam compared to phenobarbital in reducing seizure burden.
  • To evaluate the benefit of remote EEG monitoring [ Time Frame: 48 hours ]
    To prove the feasibility of centralized remote monitoring of continuous EEG monitoring in the NICU via the internet by documentation of remote accessibility of EEG recordings.
  • Evaluation of the accuracy of neonatal seizure detection algorithm [ Time Frame: 48 hours ]
    A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden.
Current Other Pre-specified Outcome Measures
 (submitted: August 12, 2019)
  • Pharmacokinetic Data [ Time Frame: 48 hours ]
    To obtain additional pharmacokinetic data "Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)" of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study.
  • Feasibility of Continuous Internet EEG Monitoring [ Time Frame: Subject study duration ]
    Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet
  • Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm [ Time Frame: 48 Hours ]
    A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden.
  • Gather Safety Information on IV Levetiracetam [ Time Frame: 5 days ]
    Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol. Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected.
Original Other Pre-specified Outcome Measures
 (submitted: October 31, 2012)
  • Pharmacokinetic Data [ Time Frame: 48 hours ]
    To obtain additional pharmacokinetic data "Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)" of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study.
  • Gather Safety Information on IV Levetiracetam [ Time Frame: 48 Hours ]
    Safety information to be collected includes any adverse events and blood parameter monitoring with Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment.
 
Descriptive Information
Brief Title  ICMJE Efficacy of Intravenous Levetiracetam in Neonatal Seizures
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Neonatal Seizures
Intervention  ICMJE
  • Drug: Intravenous levetiracetam
    Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.
    Other Name: Keppra
  • Drug: Intravenous phenobarbital
    Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.
    Other Name: phenobarbitone
Study Arms  ICMJE
  • Experimental: Intravenous levetiracetam
    Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance
    Intervention: Drug: Intravenous levetiracetam
  • Active Comparator: Intravenous phenobarbital
    Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance
    Intervention: Drug: Intravenous phenobarbital
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 9, 2018)
280
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2012)
100
Actual Study Completion Date  ICMJE July 31, 2019
Actual Primary Completion Date October 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 14 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01720667
Other Study ID Numbers  ICMJE NoGA - R01 FD004147-01A1 Haas
1R01FD004147-01A1 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard H. Haas, University of California, San Diego
Study Sponsor  ICMJE Richard H. Haas
Collaborators  ICMJE
  • University of California, San Diego
  • Rady Children's Hospital, San Diego
  • Auckland City Hospital
  • Sharp Mary Birch Hospital for Women & Newborns
  • UCSF Benioff Children’s Hospital Oakland
  • Food and Drug Administration (FDA)
Investigators  ICMJE
Principal Investigator: Richard H Haas, MD University of California, San Diego
PRS Account University of California, San Diego
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP