Levetiracetam to Prevent Post-Traumatic Epilepsy

Pavel Klein

Status and phase: Completed; Phase 2

Conditions: Post-traumatic Epilepsy; Epilepsy

Treatments: Drug: Levetiracetam

Study type: Interventional

Funder types: Other

Identifiers

NCT01463033

NS45656

Details and patient eligibility

About

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.

Enrollment: 126 patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

Levetiracetam

Active Comparator group

Description:

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.

Treatment:

Drug: Levetiracetam

No Intervention Control

No Intervention group

Description:

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.