Clinical Trial: Levetiracetam to Prevent Post-Traumatic Epilepsy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Summary:
Sponsor: Pavel Klein

Current Primary Outcome: Post-Traumatic Epilepsy [ Time Frame: 2 years ]

occurrence of PTE (Post-Traumatic Epilepsy)


Original Primary Outcome:

  • 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.


Current Secondary Outcome: 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:

  • 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 ]


Information By: Children's Research Institute

Dates:
Date Received: October 12, 2011
Date Started: April 2005
Date Completion:
Last Updated: December 11, 2015
Last Verified: December 2015