Epilepsy, Post-traumatic Epilepsy
Conditions
Keywords
Post-Traumatic epilepsy, Traumatic brain injury, Epilepsy prevention, Levetiracetam
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.
Interventions
DRUGLevetiracetam
55 mg/kg/day given in 2 divided doses 12 hours apart
Sponsors
Medstar Health Research Institute
Pavel Klein
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-Traumatic Epilepsy | 2 years | occurrence of PTE (Post-Traumatic Epilepsy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 66 |
| 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. | 60 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 4 | 4 |
Baseline characteristics
| Characteristic | Levetiracetam | Observational | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 20 Participants | 40 Participants |
| Age, Categorical >=65 years | 5 Participants | 7 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 33 Participants | 74 Participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 27 Participants |
| Sex: Female, Male Male | 50 Participants | 49 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 66 | 0 / 0 |
| serious Total, serious adverse events | 18 / 66 | 0 / 0 |
Outcome results
Primary
Post-Traumatic Epilepsy
occurrence of PTE (Post-Traumatic Epilepsy)
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Post-Traumatic Epilepsy | 6 participants |
| Observational | Post-Traumatic Epilepsy | 8 participants |
Secondary
Adverse Events
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.
Time frame: 30 day treatment period
Population: 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. Symptoms reported to be moderate or severe are listed. Adverse events were not monitored for the Observational group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Adverse Events | Suicidality | 3 Events |
| Levetiracetam | Adverse Events | Headache | 28 Events |
| Levetiracetam | Adverse Events | Fatigue | 28 Events |
| Levetiracetam | Adverse Events | Drowsiness | 20 Events |
| Levetiracetam | Adverse Events | Memory Impairment | 9 Events |
| Levetiracetam | Adverse Events | Amnesia | 8 Events |
| Levetiracetam | Adverse Events | Pain | 15 Events |
| Levetiracetam | Adverse Events | Irritability | 10 Events |
| Levetiracetam | Adverse Events | Dizziness | 10 Events |
| Levetiracetam | Adverse Events | Anorexia | 6 Events |
| Levetiracetam | Adverse Events | Emotional lability | 7 Events |
| Levetiracetam | Adverse Events | Insomnia | 5 Events |
| Levetiracetam | Adverse Events | Cognitive changes | 7 Events |
| Levetiracetam | Adverse Events | Ataxia | 6 Events |
| Levetiracetam | Adverse Events | Depression | 7 Events |
| Levetiracetam | Adverse Events | Hostility | 3 Events |
| Levetiracetam | Adverse Events | Vertigo | 1 Events |
| Levetiracetam | Adverse Events | Nausea | 2 Events |
| Levetiracetam | Adverse Events | Cough | 2 Events |
| Levetiracetam | Adverse Events | Nervousness | 5 Events |
| Levetiracetam | Adverse Events | Paraesthesia | 3 Events |
| Levetiracetam | Adverse Events | Weight gain | 1 Events |
| Levetiracetam | Adverse Events | Hallucinations | 5 Events |
| Levetiracetam | Adverse Events | Other | 2 Events |
| Levetiracetam | Adverse Events | Diplopia | 3 Events |
| Levetiracetam | Adverse Events | Psychosis | 3 Events |