Prevention of Post-traumatic Seizures With Levetiracetam

Study Overview
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Brief Summary
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Post-traumatic seizures can appear frequently after a severe traumatic brain injury. Two types of seizures are usually identified: early seizures during the week following the trauma and late epilepsy afterward. Several antiepileptic drugs are usually used to prevent early seizures but no treatment has demonstrated any preventive effect against late epilepsy. Levetiracetam is an antiepileptic drug usually used for the treatment of epileptic patients and has pharmacologic properties that could also be interesting for the prevention of post-traumatic epilepsy.

Official Title
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Prospective, Randomized, Double-blind Study Assessing the Effects of Levetiracetam Compared to Placebo in the Prevention of Early Epileptic Seizures and Late Epilepsy in Patients With Severe Traumatic Brain Injury

Conditions
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Epilepsy, Post-Traumatic

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years old Patient with severe brain injury defined as follow: Initial Glasgow Coma score (assessed on the scene of the accident) <= 8 related to the brain injury Stage 2 to 4 on the TDM US TCDB classification Initial brain CT scan performed within 48 hours after hospital admission Either a male or a nonpregnant, non-lactating female who is using adequate contraceptive method (a urine laboratory pregnancy test must be negative at baseline) Written informed consent from the patient's next-of-kin. If no relative is present as the time of inclusion, the patients will be included according to the emergency procedure Exclusion Criteria: Isolated extradural hematoma Medical decision to limit patient's care (terminal stage of a cancer, hematological malignancies, HIV, etc.) Current participation in an other protocol or within one month before study entry Previous treatment with Levetiracetam Patient's follow-up judged to be difficult by the investigator Known allergy to either Levetiracetam or products derived from pyrrolidone or one of its excipients Epileptic patient treated or not (except patients treated with benzodiazepines who can be included in this protocol)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam<br> | Drug: Levetiracetam<br>* 1500 mg/day orally until the first episode of late epilepsy for a maximum duration of 3 months<br>* Other names: Keppra;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1500 mg/day orally until the first episode of late epilepsy for a maximum duration of 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to early epileptic seizures (<= 8 days) and late epilepsy (from day 9 to 1 year) in patients with severe traumatic brain injury |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of early seizures and of late epilepsy; treatment effects according to the patient's severity, the TDM US Traumatic Coma Data Bank, and the number of regions traumatized; safety of Levetiracetam |  | One year | 
| Global prognosis (Glasgow Outcome Scale) |  | 3 months, 6 months and 1 year |