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Efficacy of Intravenous Levetiracetam in Neonatal Seizures (NEOLEV2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Description
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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.


Condition or disease Intervention/treatment Phase
Neonatal Seizures Drug: Intravenous levetiracetam Drug: Intravenous phenobarbital Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2013
Actual Primary Completion Date : October 31, 2017
Actual Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures

Arms and Interventions
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Arm Intervention/treatment
Experimental: Intravenous levetiracetam
Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance
 Drug: Intravenous levetiracetam
Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.
Other Name: Keppra
Active Comparator: Intravenous phenobarbital
Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance
 Drug: Intravenous phenobarbital
Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.
Other Name: phenobarbitone


Outcome Measures
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Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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 ]

Other Outcome Measures:
  1. 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.

  2. 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

  3. 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.

  4. 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.



Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   15 Minutes to 14 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01720667


Locations
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United States, California
University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)
San Diego, California, United States, 92103
Sponsors and Collaborators
Richard H. Haas
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
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Principal Investigator: Richard H Haas, MD University of California, San Diego
  Study Documents (Full-Text)

Documents provided by Richard H. Haas, University of California, San Diego:
Statistical Analysis Plan  [PDF] September 14, 2018
Study Protocol  [PDF] April 13, 2018

More Information
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Publications of Results:

Other Publications:

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Responsible Party: Richard H. Haas, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01720667    
Other Study ID Numbers: NoGA - R01 FD004147-01A1 Haas
1R01FD004147-01A1 ( U.S. FDA Grant/Contract )
First Posted: November 2, 2012    Key Record Dates
Results First Posted: August 21, 2019
Last Update Posted: August 21, 2019
Last Verified: August 2019
Keywords provided by Richard H. Haas, University of California, San Diego:
Seizures
Neonates
Anticonvulsants
 Treatment
Levetiracetam
Phenobarbital
Additional relevant MeSH terms:
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Seizures
Neurologic Manifestations
Nervous System Diseases
Levetiracetam
Phenobarbital
Anticonvulsants
Nootropic Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
 Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
GABA Agents
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers