Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy of Intravenous Levetiracetam in Neonatal Seizures (NEOLEV2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of California, San Diego
Sponsor:
Collaborators:
University of California, San Diego
Sharp Mary Birch Hospital San Diego CA
Rady Children's Hospital, San Diego
Auckland City Hospital, New Zealand
Children's Hospital & Research Center at Oakland, Oakland CA
Loma Linda University
Information provided by (Responsible Party):
Richard H. Haas, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01720667
First received: October 22, 2012
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Neonatal Seizures
Drug: Intravenous levetiracetam
Drug: Intravenous phenobarbital
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • To determine the efficacy of intravenous LEV in terminating neonatal seizures when given as first line therapy compared to phenobarbital [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • To obtain dose escalation data by studying the additional efficacy of a further dose in non responders. [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Pharmacokinetic Data [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 100
Study Start Date: March 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 2 randomized blinded controlled study.

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
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 >37 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 1.2mM
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720667

Contacts
Contact: Richard H Haas, MD 858-966-5819 rhaas@ucsd.edu
Contact: Gail E Reiner, DNP, FNP-C 858-966-5819 gereiner@ucsd.edu

Locations
United States, California
University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU) Recruiting
San Diego, California, United States, 92103
Contact: Richard H Haas, MD    858-822-6700    rhaas@ucsd.edu   
Contact: Gail E Reiner, DNP, FNP-C    619-471-9134    gereiner@ucsd.edu   
Principal Investigator: Richard H Haas, MD         
Sponsors and Collaborators
Richard H. Haas
University of California, San Diego
Sharp Mary Birch Hospital San Diego CA
Rady Children's Hospital, San Diego
Auckland City Hospital, New Zealand
Children's Hospital & Research Center at Oakland, Oakland CA
Loma Linda University
Investigators
Principal Investigator: Richard H Haas, MD University of California, San Diego
  More Information

Publications:
Responsible Party: Richard H. Haas, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01720667     History of Changes
Other Study ID Numbers: NoGA - R01 FD004147-01A1 Haas, NoGA - R01 FD004147-01A1 Haas
Study First Received: October 22, 2012
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
Seizures
Neonates
Anticonvulsants
Treatment
Levetiracetam
Phenobarbital

Additional relevant MeSH terms:
Seizures
Brain Diseases
Central Nervous System Diseases
Epilepsy
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Etiracetam
Phenobarbital
Piracetam
Anticonvulsants
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Nootropic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014