Prevention of Post-traumatic Seizures With Levetiracetam (TRACK)

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

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.

Study Overview

• Status: Terminated
• Conditions: Epilepsy, Post-Traumatic
• Intervention / Treatment: Drug: Levetiracetam; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France
    • Neurologie - CHU Angers
  • Bordeaux, France
    • Neurology - CHU Bordeaux
  • Caen, France
    • Neurologie - CHU Caen
  • Grenoble, France
    • Neurochirurgie-CHU Grenoble
  • Grenoble, France
    • Neurology - CHU Rennes
  • Lille, France
    • Neurophysiologie Clinique - CHU Lille
  • Lyon, France
    • Neurophysiologie clinique - CHU Lyon (Hôpital neurologique)
  • Marseille, France
    • Beurophysiologie clinique - CHU Marseille
  • Montpellier, France
    • Epileptologie - CHU Montpellier
  • Nancy, France
    • Neurologie - CHU Nancy
  • Paris, France, 75674
    • Neurochirurgie-Paris Saint Anne
  • Rennes, France, 35000
    • Neurologie - CHU Rennes
  • Rennes, France
    • Explorations Fonctionnelles Neurologiques - CHU Nantes
  • Rouen, France
    • Neurologie - CHU Rouen
  • Tours, France
    • Neurologie - CHU Tours Hopital Trousseau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age >= 18 years old

2. 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
3. Initial brain CT scan performed within 48 hours after hospital admission
4. 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)
5. 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:

1. Isolated extradural hematoma
2. Medical decision to limit patient's care (terminal stage of a cancer, hematological malignancies, HIV, etc.)
3. Current participation in an other protocol or within one month before study entry
4. Previous treatment with Levetiracetam
5. Patient's follow-up judged to be difficult by the investigator
6. Known allergy to either Levetiracetam or products derived from pyrrolidone or one of its excipients
7. Epileptic patient treated or not (except patients treated with benzodiazepines who can be included in this protocol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: UCB Pharma
• Investigators: Study Chair: Bruno Laviolle, MD, Rennes University Hospital; Principal Investigator: Arnaud Biraben, MD, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: November 29, 2007
• First Submitted That Met QC Criteria: November 29, 2007
• First Posted (Estimate): November 30, 2007

Study Record Updates

• Last Update Posted (Estimate): June 21, 2012
• Last Update Submitted That Met QC Criteria: June 20, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Epilepsy; Seizures; Epilepsy, Post-Traumatic; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: EudraCT: 2006-006518-13; CIC0203/60 (Other Identifier: Rennes University Hospital); LOC/06-06 (Other Identifier: Rennes University Hospital)