Assess Safety and Efficacy of Levetiracetam(LEV;Keppra)for Seizure Prevention

Study Overview
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Brief Summary
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To show that the use of intravenous levetiracetam(LEV;Keppra)for seizure prevention in patients in the Neuroscience Intensive Care Unit will result in fewer side effects compared to the current standard of care anticonvulsant and will be at least as effective as the current standard of care in preventing clinical and sub-clinical seizure activity.

Detailed Description
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To show that the use of intravenous levetiracetam(LEV;Keppra)for seizure prophylaxis in the Neuroscience Intensive Care Unit will result in fewer adverse effects compared to the current standard of care anticonvulsant(phenytoin) and will be at least as effective as phenytoin in preventing clinical and sub-clinical seizure activity.

Official Title
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Assessment of Seizure Prophylaxis Protocols Using Intravenous Levetiracetam in a Neuroscience Intensive Care Unit

Conditions
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Traumatic Brain Injury, Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Phenytoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with traumatic brain injury Glasgow Coma Score (GCS) score 3-8(inclusive),or GCS motor score of 5 or less and abnormal admission CT scan showing intracranial pathology Hemodynamically stable with a systolic BP >90 mm Hg At least one reactive pupil A negative pregnancy test in females Age at least 18 years Signed informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for research form OR Subjects with subarachnoid hemorrhage (SAH) SAH documented by CT scan Hunt-Hess grade 3-5, inclusive Hemodynamically stable with a systolic BP> 90 mm Hg At least one reactive pupil A negative pregnancy test in females Age of at least 18 years Signed informed consent and HIPAA authorization for research form Exclusion Criteria for enrollment No venous access Spinal cord injury History of or CT confirmation of previous brain injury such as brain tumor, cerebral infarct, or spontaneous intracerebral hemorrhage Hemodynamically unstable Suspected anoxic events Other peripheral trauma likely to result in liver failure Positive pregnancy test in females Age less than 18 years of age Known hypersensitivity to any anticonvulsant An injury that, in the opinion of the principal investigator, has a high likelihood of death within the first 72 hours. Any treatment, condition, or injury that contraindicates treatment with LEV (levetiracetam) or phenytoin (PHT). Inability to obtain signed informed consent or HIPAA authorization for research.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levetiracetam<br>Group 1 - The levetiracetam (Keppra®) group will receive a loading dose of 20 mg/kg IV over 15 minutes (rounded to the nearest 250mg) up to a maximum of 2000 mg, then started on maintenance dose (1000 mg, IV BID)as prophylaxis for 7 days. | Drug: Levetiracetam<br>* Levetiracetam group will receive a loading dose of 20 mg/kg IV(rounded to nearest 250mg) to a maximum of 2000mg, then started on maintenance dose (1000 mg,IV q 12h) as prophylaxis for seven days.<br>* Other names: Keppra;|
| Active Comparator: Phenytoin<br>Group 2-The phenytoin group will receive a loading dose of 20 mg/kg IV to a maximum of 2000mg, then started on maintenance dose at 5 mg/kg/day (rounded to nearest 100mg dose, IV, divided into three doses a day) as prophylaxis for 7 days. Phenytoin levels are to be checked daily and dose adjusted as needed to maintain therapeutic levels of 10-20 µg/dL. | Drug: Phenytoin<br>* The group will receive a loading dose of fosphenytoin 20 mg/kg IV to a maximum of 2000 mg, then started on maintenance dose of 5mg/kg/day, rounded to nearest 100mg dose, IV, q 12h for seven days.<br>* Other names: Dilantin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure Incidence | This was the number of patients in each group who demonstrated seizure activity during the course of the study | Duration of study, up to 6 months after the injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extended Glasgow Outcome Score | This is an 8 point validated scale that measures disability after brain injury. It is assessed through an in person exam or by phone interview at hospital discharge, 3 months and 6 months after injury. The categories are: 1 = dead; 2 = vegetative state; 3 = severe disability, low level; 4 = severe disability, high level; 5 = moderate disability, low level; 6 = moderate disability, high level; 7 = good recovery - low level; 8 = good recovery - high level. Specific questions and activities are assessed to determine into which category the patient falls. | at discharge; 3 and 6 months following injury | 
| Disability Rating Scale (DRS) | The Disability rating scale (DRS) is frequently used in the rehabilitation literature as a measure of disability. It is a reliable, easily performed test that assesses 8 items (eye opening, verbalization, motor response, feeding, toileting, grooming, level of functioning, employability), and assigns each a numerical score ranging from 0 - 5 based on the category. The domains these 8 items are felt to assess include: alertness, cognition for self-care, dependence, and psychosocial adaptability. The scoring range is from 0-30, with increasing disability levels assigned to higher numerical values. The total DRS is then dichotomized into favorable (disability = none, mild, partial or moderate disability) and unfavorable (disability = moderately severe, severe, extremely severe, vegetative state, extreme vegetative state, death) outcomes. A DRS score of 0-6 was favorable, with any score greater than 6 categorized as unfavorable. | Discharge; 3 and 6 months following injury | 
| Incidence of Adverse Events |  | discharge; 3 and 6 months following injury | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Seizures, Traumatic Brain Injury, Subarachnoid Hemorrhage