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

Phase 4

Completed

• Conditions: Traumatic Brain Injury; Subarachnoid Hemorrhage
• Interventions: Drug: Phenytoin; Drug: Levetiracetam

• Registration Number: NCT00618436
• Lead Sponsor: University of Cincinnati

Brief Summary

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

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.

Study Timeline

• Study Start: 2007-08
• Study First Submitted: 2008-02-08
• Study First Submitted QC: 2008-02-19
• Study First Posted: 2008-02-20
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Results First Submitted: 2013-08-29
• Status Verified: 2014-03
• Results First Submitted QC: 2014-03-07
• Last Update Submitted: 2014-03-07
• Results First Posted: 2014-04-07
• Last Update Posted: 2014-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phenytoin	Phenytoin	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.
Levetiracetam	Levetiracetam	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.

Primary Outcome Measures

Name	Time	Method
Seizure Incidence	Duration of study, up to 6 months after the injury	This was the number of patients in each group who demonstrated seizure activity during the course of the study

Secondary Outcome Measures

Name	Time	Method
Extended Glasgow Outcome Score	at discharge; 3 and 6 months following injury	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.
Disability Rating Scale (DRS)	Discharge; 3 and 6 months following injury	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.
Incidence of Adverse Events	discharge; 3 and 6 months following injury

Trial Locations

Locations (1)

University of Cincinnati Hospital; 🇺🇸 Cincinnati, Ohio, United States