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

• ClinicalTrials.gov Identifier: NCT00618436
• Recruitment Status: Completed
• First Posted: February 20, 2008
• Results First Posted: April 7, 2014
• Last Update Posted: April 7, 2014
• Sponsor: University of Cincinnati
• Collaborator: Mayfield Clinic & Spine Institute
• Information provided by (Responsible Party): Lori Shutter, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Traumatic Brain Injury; Subarachnoid Hemorrhage	Drug: Levetiracetam; Drug: Phenytoin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Assessment of Seizure Prophylaxis Protocols Using Intravenous Levetiracetam in a Neuroscience Intensive Care Unit
• Study Start Date: August 2007
• Actual Primary Completion Date: September 2009
• Actual Study Completion Date: September 2009

Arms and Interventions

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 Name: 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 Name: Dilantin

Outcome Measures

Primary Outcome Measures :

1. Seizure Incidence [ Time Frame: 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 :

1. Extended Glasgow Outcome Score [ Time Frame: 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.
2. Disability Rating Scale (DRS) [ Time Frame: 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.
3. Incidence of Adverse Events [ Time Frame: discharge; 3 and 6 months following injury ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Ohio

University of Cincinnati Hospital

Cincinnati, Ohio, United States, 45220

Sponsors and Collaborators

University of Cincinnati

Mayfield Clinic & Spine Institute

Investigators

• Principal Investigator: Lori Shutter, MD; University of Pittsburgh

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Lori Shutter, Director, Neurocritical Care Fellowship Program, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00618436
• Other Study ID Numbers: 06-4-6-7
• First Posted: February 20, 2008
• Results First Posted: April 7, 2014
• Last Update Posted: April 7, 2014
• Last Verified: March 2014

Keywords provided by Lori Shutter, University of Pittsburgh:

Seizures; Traumatic Brain Injury; Subarachnoid Hemorrhage

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Seizures; Subarachnoid Hemorrhage; Hemorrhage; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Pathologic Processes; Neurologic Manifestations; Intracranial Hemorrhages; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Phenytoin; Levetiracetam; Anticonvulsants; Nootropic Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers