Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures (Keppra)

This study has been completed.
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Richard H. Haas, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00884052
First received: April 17, 2009
Last updated: October 21, 2012
Last verified: October 2012
  Purpose

The hypothesis is that a loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg of Levetiracetam is going to be safe and effective in the treatment of seizures in neonates.


Condition Intervention Phase
Seizures
Disorder of Fetus or Newborn
Drug: levetiracetam
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Pharmacokinetic profile [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The primary intent of the data analysis is to determine levetiracetam pharmacokinetics in newborn infants and predict the dosage necessary to maintain concentrations similar to those seen with effective therapy in other populations. Graphs of serum concentration vs. time will be plotted for levetiracetam for each infant. Mean serum drug concentration vs. time curves will also be constructed. Summary statistics (i.e., n, mean, standard deviation, minimum, maximum, and coefficient of variation) will be calculated for serum concentrations for each time point and each dose level.


Enrollment: 18
Study Start Date: April 2007
Study Completion Date: October 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: levetiracetam dose escalation
Escalation of dose after 6 patients treated to 40 mg/kg IV load and 10mg/kg/day maintenance
Drug: levetiracetam
20 mg/kg loading dose; 5 mg/kg daily for 7 days.
Other Name: Keppra
Drug: levetiracetam
40 mg/kg IV load; 10 mg/kg/day maintenance
Other Name: Keppra

Detailed Description:

In adults, drug clearance is less than half of the glomerular filtration rate and the drug half-life is 6-8 hours. Renal function in infants at birth is characterized by immature glomerular filtration and is only 20% that of older children. The specific esterase responsible for levetiracetam hydrolysis has not been identified and its expression in newborn infants is unknown. Depending on its activity, the expected infant total levetiracetam clearance will likely be between 15-45% of older populations. However, due to immaturity in levetiracetam clearance in infants, accumulation with multiple dosing is possible. Therefore the maintenance dose is reduced compared to older children according to the anticipated impaired clearance.

These anticipated differences in levetiracetam clearance and volume of distribution, will likely result in a prolonged drug half-life of 10-30 hours in infants. This prolonged elimination will require longer sampling to adequately characterize levetiracetam pharmacodynamics in this population.

The primary intent of the data analysis is to determine levetiracetam pharmacokinetics in newborn infants and predict the dosage necessary to maintain concentrations similar to those seen with effective therapy in other populations. Graphs of serum concentration vs. time will be plotted for levetiracetam for each infant. Mean serum drug concentration vs. time curves will also be constructed. Summary statistics (i.e., n, mean, standard deviation, minimum, maximum, and coefficient of variation) will be calculated for serum concentrations for each time point and each dose level.

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newborns admitted to the UCSD, Children's Hospital or Sharp Mary Birch NICUs with seizures.
  • Term infants (gestational age greater than or equal to 37 weeks.
  • > 2500 grams (max blood for study 6mL =3%).
  • Postnatal age < 14 days.
  • Serum creatinine less than 1.2 at time of enrollment.
  • Received loading dose of phenobarbital 20mg/kg.
  • Are still experiencing either clinical or electroencephalographic seizures despite this therapy.
  • For whom parental consent to participate in the study is obtained.

Exclusion Criteria:

  • Biochemical abnormality - hypoglycemia, hypocalcemia-that when treated result in seizure cessation.
  • Severe hypoxic ischemic injury likely to result in imminent death
  • The only significant exclusions that will be made in recruitment and enrollment will be the exclusion of infants who are judged by the attending neonatologist to be so critically ill that death is imminent and benefit from neonatal intensive care is very unlikely.
  • No rule-based criteria, (using lab or clinical parameters) adequately capture the complete nature of this clinical assessment.
  • In general any child receiving active treatment with head cooling will not be excluded.
  • Mechanical ventilation and/or the use of inotropic agents to support blood pressure will not be exclusion criteria.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00884052

Locations
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
Thrasher Research Fund
Investigators
Principal Investigator: Richard Haas, MD University of Calfornia, San Diego
  More Information

Publications:
Responsible Party: Richard H. Haas, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00884052     History of Changes
Other Study ID Numbers: Thrasher 02825-1
Study First Received: April 17, 2009
Last Updated: October 21, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
Neonatal seizures

Additional relevant MeSH terms:
Seizures
Fetal Diseases
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Pregnancy Complications
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 September 16, 2014