IV Levetiracetam for the Treatment of Neonatal Seizures: a Pharmacokinetic and Preliminary Efficacy and Safety Study

This study has been completed.
Sponsor:
Collaborators:
Pediatric Pharmacology Research Units Network
Thrasher Research Fund
Information provided by (Responsible Party):
Richard H. Haas, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00461409
First received: April 16, 2007
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to determine the correct dosing for intravenous levetiracetam in term new born babies with seizures. In addition information on safety and efficacy will be collected. This new anticonvulsant drug is a promising treatment for seizures in newborns.


Condition Intervention Phase
Seizures
Term Neonates
Drug: Intravenous levetiracetam
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of IV Levetiracetam as an add-on Drug for Seizures in Term Neonates Assessing Pharmacokinetics, Safety and Efficacy.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Pharmacokinetic data on intravenous levetiracetam administered to term neonates over 7 days. [ Time Frame: Study completion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Preliminary safety data and efficacy data will be collected. [ Time Frame: Study completion ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: April 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Intravenous levetiracetam
    IV levetiracetam escalating to 40mg/kg load and daily 10mg/kg maintenance
    Other Name: Keppra
Detailed Description:

There is a pressing need to improve the treatment of seizures in the neonatal period. The anticonvulsant agents currently in use may damage the developing brain and are quite ineffective at controlling seizures in neonates. Newborn seizures are common (1 in 300 newborns) and are associated with very poor outcomes. 20-30% of infants with neonatal seizures die, 20-30% develop epilepsy outside the neonatal period and 20-40% develop cerebral palsy and/or mental retardation. Better treatments for neonatal seizures could improve these outcomes.

An intravenous form of the anti-seizure medication levetiracetam has been released for use in adults with epilepsy. Experience with oral levetiracetam has shown it to be a very safe medication, with good efficacy in stopping seizures in other age groups. The intravenous preparation could allow its use in neonates with seizures. Drug handling by the body is very different in neonates to adults. Before we can use levetiracetam in this age group we need to determine the correct dose and frequency by studying its absorption and distribution in the body (pharmacokinetic profile).

This study is an add-on open label pharmacokinetic and preliminary safety study. Twenty-four patients with neonatal seizures, who still experience clinical or electroencephalographic seizures after treatment with Phenobarbital will be treated with intravenous levetiracetam, and serial determinations of serum levetiracetam levels will be made to allow calculation of pharmacokinetic parameters. We will also collect preliminary safety data. We will specifically monitor for abnormalities of heart rate, respiratory rate and blood pressure, unexpected death, the occurrence of hypotonia, sedation, poor feeding, irritability or infection. Blood tests monitoring blood, liver and kidney function will be checked at baseline, 48 hours and at completion of 7 days of treatment. We will also collect preliminary descriptive data on the efficacy of levetiracetam in stopping neonatal seizures.

  Eligibility

Ages Eligible for Study:   37 Weeks to 42 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newborns admitted with seizures to the UCSD, Children's Hospital or Sharp Mary Birch NICUs in San Diego, CA, USA as well as Auckland City Hospital, Grafton,Auckland NZ :
  • Term infants (gestational age greater than or equal to 37 weeks > 2460 grams (max blood for study 6mL =3%)
  • Postnatal age < 14 days.
  • Received loading dose of phenobarbital 20mg/kg and/or phenytoin.
  • Ongoing clinical or electroencephalographic seizures despite this therapy.
  • For whom parental consent to participate in the study is obtained.

Exclusion Criteria:

  • Serum creatinine greater than 1.2 at enrollment or greater than 2.0 at any time.
  • Biochemical abnormality - hypoglycemia, hypocalcemia- that when treated result in seizure cessation.
  • Severe hypoxic ischemic injury likely to result in imminent death
  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: NCT00461409

Locations
United States, California
UCSD Hillcrest Medical Center
San Diego, California, United States, 92103
Sharpe Mary Birch Hospital
San Diego, California, United States, 92123
New Zealand
Auckland City Hospital
Auckland, New Zealand
Sponsors and Collaborators
Richard H. Haas
Pediatric Pharmacology Research Units Network
Thrasher Research Fund
Investigators
Principal Investigator: Richard Haas, MBBChir University of California, San Diego
  More Information

No publications provided

Responsible Party: Richard H. Haas, Professor of Neurosciences and Pediatrics, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00461409     History of Changes
Other Study ID Numbers: NeoLev 1
Study First Received: April 16, 2007
Last Updated: February 2, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
Neonatal Seizures
Treatment
Anticonvulsant
Levetiracetam

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Etiracetam
Piracetam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014