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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
Results First Posted : March 26, 2020
Last Update Posted : March 26, 2020
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Richard H. Haas, University of California, San Diego

Study Description
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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.

Condition or disease Intervention/treatment Phase
Seizures Disorder of Fetus or Newborn Drug: Low dose levetiracetam Drug: High dose levetiracetam Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
Study Start Date : April 2007
Actual Primary Completion Date : March 2011
Actual Study Completion Date : October 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures

Arms and Interventions
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Arm Intervention/treatment
Experimental: levetiracetam dose escalation
6 Babies in Phase 1-Received Dose 1: 20 mg/kg; 5 mg/kg daily 12 Babies in Phase 2-Received Dose 2: 40 mg/kg; 10 mg/kg/day
 Drug: Low dose levetiracetam
20 mg/kg loading dose; 5 mg/kg daily for 7 days.
Other Name: Keppra

Drug: High dose levetiracetam
40 mg/kg IV load; 10 mg/kg/day maintenance
Other Name: Keppra


Outcome Measures
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Primary Outcome Measures :
  1. Drug Clearance [ Time Frame: Day 1 and Day 7 ]
  2. Drug Half Life [ Time Frame: Day 1 and Day 7 ]

Secondary Outcome Measures :
  1. Levetiracetam Treated Number of Participants With Serious Adverse Events [ Time Frame: 7 Days ]

Eligibility Criteria
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Ages Eligible for Study:   up to 14 Days   (Child)
Sexes Eligible for Study:   All
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 or less.
  • 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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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00884052


Locations
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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
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Principal Investigator: Richard Haas, MD University of Calfornia, San Diego
More Information
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Publications of Results:

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Responsible Party: Richard H. Haas, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00884052    
Obsolete Identifiers: NCT00461409
Other Study ID Numbers: Thrasher 02825-1
First Posted: April 20, 2009    Key Record Dates
Results First Posted: March 26, 2020
Last Update Posted: March 26, 2020
Last Verified: March 2020
Keywords provided by Richard H. Haas, University of California, San Diego:
Neonatal seizures
Additional relevant MeSH terms:
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Seizures
Fetal Diseases
Neurologic Manifestations
Nervous System Diseases
 Pregnancy Complications
Levetiracetam
Anticonvulsants
Nootropic Agents