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

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

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Levetiracetam; Drug: Phenytoin

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 Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • University of Cincinnati Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 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.	Drug: Levetiracetam; 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.; Other Names: Keppra
ACTIVE_COMPARATOR: 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.	Drug: Phenytoin; 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.; Other Names: Dilantin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Mayfield Clinic & Spine Institute
• Investigators: Principal Investigator: Lori Shutter, MD, University of Pittsburgh

Publications and helpful links

General Publications

• Steinbaugh LA, Lindsell CJ, Shutter LA, Szaflarski JP. Initial EEG predicts outcomes in a trial of levetiracetam vs. fosphenytoin for seizure prevention. Epilepsy Behav. 2012 Mar;23(3):280-4. doi: 10.1016/j.yebeh.2011.12.005. Epub 2012 Feb 16.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): September 1, 2009
• Study Completion (ACTUAL): September 1, 2009

Study Registration Dates

• First Submitted: February 8, 2008
• First Submitted That Met QC Criteria: February 19, 2008
• First Posted (ESTIMATE): February 20, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 7, 2014
• Last Update Submitted That Met QC Criteria: March 7, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Subarachnoid Hemorrhage; Seizures; Traumatic Brain Injury
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Brain Injuries; Hemorrhage; Brain Injuries, Traumatic; Seizures; Subarachnoid Hemorrhage; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Nootropic Agents; Levetiracetam; Phenytoin
• Other Study ID Numbers: 06-4-6-7