Levetiracetam to Prevent Post-Traumatic Epilepsy

Phase 2

Completed

• Conditions: Epilepsy; Post-traumatic Epilepsy
• Interventions: Drug: Levetiracetam

• Registration Number: NCT01463033
• Lead Sponsor: Pavel Klein

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 available

Study Timeline

• Study Start: 2005-04
• Primary Completion: 2008-06
• Study Completion: 2010-02
• Study First Submitted: 2011-10-12
• Study First Submitted QC: 2011-10-28
• Study First Posted: 2011-11-01
• Results First Submitted: 2014-11-11
• Results First Submitted QC: 2015-10-01
• Results First Posted: 2015-11-01
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-11
• Last Update Posted: 2016-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 126

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Levetiracetam	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.

Primary Outcome Measures

Name	Time	Method
Post-Traumatic Epilepsy	2 years	occurrence of PTE (Post-Traumatic Epilepsy)

Secondary Outcome Measures

Name	Time	Method
Adverse Events	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.

Trial Locations

Locations (2)

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

MedStar Research Institute; 🇺🇸 Washington, District of Columbia, United States