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Levetiracetam to Prevent Post-Traumatic Epilepsy

This study has been completed.
Sponsor:
Collaborator:
Medstar Research Institute
Information provided by (Responsible Party):
Children's Research Institute
ClinicalTrials.gov Identifier:
NCT01463033
First received: October 12, 2011
Last updated: October 28, 2011
Last verified: October 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Epilepsy
Post-traumatic Epilepsy
 Drug: Levetiracetam
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pilot: Levetiracetam to Prevent Post-Traumatic Epilepsy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • adverse effect profile [ Time Frame: One month ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Subject enrollment [ Time Frame: 0-8 and 8-24 hours after injury ] [ Designated as safety issue: No ]
  • Subject retention [ Time Frame: days 3,7,14,30,60 and months 6,9,12,18 and 242 after injury ] [ Designated as safety issue: No ]
  • Treatment compliance [ Time Frame: Treatment days 3,7,14 and 30 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 126
Study Start Date: April 2005
Study Completion Date: February 2010
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 Drug: Levetiracetam
55 mg/kg/day given in 2 divided doses 12 hours apart
Other Name: Keppra (brand name)
No Intervention: Observational
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.
 Drug: Levetiracetam
55 mg/kg/day given in 2 divided doses 12 hours apart
Other Name: Keppra (brand name)

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • Male and female subjects aged ≥ 6 years.

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01463033

Locations
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
MedStar Research Institute
Washington, District of Columbia, United States, 20010
Sponsors and Collaborators
Children's Research Institute
Medstar Research Institute
Investigators
Principal Investigator: Pavel Klein, M.D. Children's Research Institute
  More Information

No publications provided by Children's Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Children's Research Institute
ClinicalTrials.gov Identifier: NCT01463033     History of Changes
Other Study ID Numbers: NS45656
Study First Received: October 12, 2011
Last Updated: October 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Research Institute:
Post-Traumatic epilepsy
Traumatic brain injury
Epilepsy prevention
Levetiracetam

Additional relevant MeSH terms:
Epilepsy
Epilepsy, Post-Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Injuries
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
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 May 22, 2013