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

April 16, 2007
February 2, 2012
April 2007
March 2011   (final data collection date for primary outcome measure)
Pharmacokinetic data on intravenous levetiracetam administered to term neonates over 7 days. [ Time Frame: Study completion ] [ Designated as safety issue: No ]
Pharmacokinetic data on intravenous levetiracetam administered to term neonates over 7 days.
Complete list of historical versions of study NCT00461409 on ClinicalTrials.gov Archive Site
Preliminary safety data and efficacy data will be collected. [ Time Frame: Study completion ] [ Designated as safety issue: Yes ]
Preliminary safety data and efficacy data will be collected.
Not Provided
Not Provided
 
IV Levetiracetam for the Treatment of Neonatal Seizures: a Pharmacokinetic and Preliminary Efficacy and Safety Study
Phase I/II Study of IV Levetiracetam as an add-on Drug for Seizures in Term Neonates Assessing Pharmacokinetics, Safety and Efficacy.

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Seizures
  • Term Neonates
Drug: Intravenous levetiracetam
IV levetiracetam escalating to 40mg/kg load and daily 10mg/kg maintenance
Other Name: Keppra
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
March 2011
March 2011   (final data collection date for primary outcome measure)

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
Both
37 Weeks to 42 Weeks
No
Contact information is only displayed when the study is recruiting subjects
United States,   New Zealand
 
NCT00461409
NeoLev 1
Yes
Richard H. Haas, University of California, San Diego
Richard H. Haas
  • Pediatric Pharmacology Research Units Network
  • Thrasher Research Fund
Principal Investigator: Richard Haas, MBBChir University of California, San Diego
University of California, San Diego
February 2012

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