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

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ClinicalTrials.gov Identifier: NCT00884052
Recruitment Status : Completed
First Posted : April 20, 2009
Last Update Posted : October 23, 2012
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Richard H. Haas, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE April 17, 2009
First Posted Date  ICMJE April 20, 2009
Last Update Posted Date October 23, 2012
Study Start Date  ICMJE April 2007
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2010)
Pharmacokinetic profile [ Time Frame: 18 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2009)
Pharmacokinetic profile [ Time Frame: 18 months ]
Change History Complete list of historical versions of study NCT00884052 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
Official Title  ICMJE Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Seizures
  • Disorder of Fetus or Newborn
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: levetiracetam dose escalation
Escalation of dose after 6 patients treated to 40 mg/kg IV load and 10mg/kg/day maintenance
Interventions:
  • Drug: levetiracetam
  • Drug: levetiracetam
Publications * Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2012)
18
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2009)
24
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 14 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00884052
Other Study ID Numbers  ICMJE Thrasher 02825-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard H. Haas, University of California, San Diego
Study Sponsor  ICMJE Richard H. Haas
Collaborators  ICMJE Thrasher Research Fund
Investigators  ICMJE
Principal Investigator: Richard Haas, MD University of Calfornia, San Diego
PRS Account University of California, San Diego
Verification Date October 2012

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