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Levetiracetam to Prevent Post-Traumatic Epilepsy

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ClinicalTrials.gov Identifier: NCT01463033
Recruitment Status : Completed
First Posted : November 1, 2011
Results First Posted : November 2, 2015
Last Update Posted : January 13, 2016
Sponsor:
Collaborator:
Medstar Health Research Institute
Information provided by (Responsible Party):
Pavel Klein, Children's Research Institute

Tracking Information
First Submitted Date  ICMJE October 12, 2011
First Posted Date  ICMJE November 1, 2011
Results First Submitted Date  ICMJE November 11, 2014
Results First Posted Date  ICMJE November 2, 2015
Last Update Posted Date January 13, 2016
Study Start Date  ICMJE April 2005
Actual Primary Completion Date June 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2015)
Post-Traumatic Epilepsy [ Time Frame: 2 years ]
occurrence of PTE (Post-Traumatic Epilepsy)
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2011)
  • adverse effect profile [ Time Frame: One month ]
    AE outcome measures included (1) proportion of LEV-treated subjects with medication-related SAEs, (2) proportion of LEV-treated subjects who stopped treatment because of AEs (3) AE score, using a quantified scale of symptom severity and frequency; (4) comparison of serious infection (defined as any antibiotic-treated infection) between LEV-treated and observational groups; and (5)comparison between LEV treated and observational groups of proportion of abnormal scores on mood questionnaires using the Achenbach System of Empirically Based Assessment (ASEBA) and CSCD depression.
  • pharmacokinetic profile of levetiracetam [ Time Frame: treatment day 3 ]
    PK outcome measures included C-max, T-max and area under curve using blood samples at 30 minutes, 1,2,3,4,6,8,and 12 hours after LEV administration.
  • pharmacokinetic profile of levetiracetam administered during the acute and chronic phase of head injury orally, intravenously and via orogastric tube [ Time Frame: Treatment day 30 ]
    PK outcome measures included C-max, T-max and area under curve using blood samples at 30 minutes, 1,2,3,4,6,8,and 12 hours after LEV administration.
Change History Complete list of historical versions of study NCT01463033 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2015)
Adverse Events [ Time Frame: 30 day treatment period ]
The 66 subjects with acute head injury with a high risk for developing post-traumatic epilepsy that received levetiracetam 55 mg/kg/day in a b.i.d. were monitored for adverse events through the 30 day treatment period.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2011)
  • Subject enrollment [ Time Frame: 0-8 and 8-24 hours after injury ]
  • Subject retention [ Time Frame: days 3,7,14,30,60 and months 6,9,12,18 and 242 after injury ]
  • Treatment compliance [ Time Frame: Treatment days 3,7,14 and 30 ]
    Treatment compliance outcome measures included comparison of pill count/liquid volume comparing the number of pills/amount of liquid dispensed with the number/volume returned at each visit; and (2) serum levetiracetam levels of <2 mcg/ml on study/treatment days 2, 3,4 7, 14 and 30.
  • post-traumatic epilepsy [ Time Frame: 2 years after injury ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Levetiracetam to Prevent Post-Traumatic Epilepsy
Official Title  ICMJE Pilot: Levetiracetam to Prevent Post-Traumatic Epilepsy
Brief Summary Head injury is the cause of approximately 5% of all epilepsy in the US. Past attempts at preventing epilepsy by treatment with older antiepileptic drugs have been unsuccessful. Levetiracetam is a novel AED with potent antiepileptogenic properties in animal models of epilepsy. It has a favorable side effect and pharmacokinetic profile. It is therefore a strong candidate for a clinical trial of epilepsy prevention following traumatic brain injury (TBI). However, there has been no experience in administering levetiracetam rapidly to individuals with acute TBI. The investigators propose to initiate the evaluation of levetiracetam in prevention of post-traumatic epilepsy by determining the safety, tolerability, pharmacokinetics and feasibility of acute and chronic administration of levetiracetam to individuals with head injury with a high risk for developing post-traumatic epilepsy. Further, the investigators will follow subjects for 2 years after injury in order to obtain pilot data about effect of levetiracetam on PTE. This pilot study is the first step in evaluation of levetiracetam in prevention of post-traumatic epilepsy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Epilepsy
  • Post-traumatic Epilepsy
Intervention  ICMJE Drug: Levetiracetam
55 mg/kg/day given in 2 divided doses 12 hours apart
Other Name: Keppra (brand name)
Study Arms  ICMJE
  • Active Comparator: Levetiracetam
    66 subjects with acute head injury with a high risk for developing post-traumatic epilepsy will receive levetiracetam 55 mg/kg/day in a b.i.d. schedule. Treatment will commence within 8 hours of the acute head injury and will last for 30 days. In addition, subjects will receive phenytoin for 1 week following head injury as standard clinical care.
    Intervention: Drug: Levetiracetam
  • No Intervention: No Intervention Control
    60 subjects with acute head injury with a high risk for developing post-traumatic epilepsy enrolled 8-24 hours after injury will not receive levetiracetam. Subjects will receive phenytoin for 1 week following head injury as standard clinical care.
Publications *

*   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 28, 2011)
126
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date June 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Acute head injury associated with one of the following:

Intracranial hemorrhage, including epidural, subdural and intracerebral hemorrhage or with cerebral contusion(s) of any size; Penetrating (foreign body) head injury; Skull fracture and dural tear; Seizure within 8 hours of head injury

  • Onset of head injury within 8-hours of proposed treatment initiation.
  • Glasgow Coma Scale 6-15.

Exclusion Criteria:

  • Clinical contraindications:

    • Previous epilepsy or status epilepticus.
    • Any systemic illness or unstable medical condition that might pose additional risk, including: renal insufficiency, other unstable metabolic or endocrine disturbances, and active systemic cancer.
    • Psychosis within six months of enrollment as determined by history of hospitalization for psychosis or medications for psychosis.
    • Moderate to severe mental retardation (IQ< 55 or>2 school grade levels below the expected for age [expected age = grade level +5]).
  • Clinical/Laboratory Indicators:

    • Serum creatinine > 1.5 on the day of treatment initiation for adults.
    • Serum creatinine ≥1.5 for subjects ≥17 years old, ≥1.0 for subjects 13-17 years old and ≥0.7 for subjects 6-12 years old.
    • Pregnancy
    • Use of any CNS-active investigational drugs within 3 months of enrollment.
    • Use of Antiepileptic Drugs (AEDs) within two months of enrollment, for any indication.
    • Allergy/sensitivity to study drugs or their formulations:
    • Active drug or alcohol dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements:
    • Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
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 NCT01463033
Other Study ID Numbers  ICMJE NS45656
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pavel Klein, Children's Research Institute
Study Sponsor  ICMJE Pavel Klein
Collaborators  ICMJE Medstar Health Research Institute
Investigators  ICMJE
Principal Investigator: Pavel Klein, M.D. Children's Research Institute
PRS Account Children's Research Institute
Verification Date December 2015

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