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

This study has been completed.
Sponsor:
Collaborator:
Mayfield Clinic & Spine Institute
Information provided by (Responsible Party):
Lori Shutter, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00618436
First received: February 8, 2008
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Traumatic Brain Injury
Subarachnoid Hemorrhage
Drug: Levetiracetam
Drug: Phenytoin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessment of Seizure Prophylaxis Protocols Using Intravenous Levetiracetam in a Neuroscience Intensive Care Unit

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • Seizure Incidence [ Time Frame: Duration of study, up to 6 months after the injury ] [ Designated as safety issue: No ]
    This was the number of patients in each group who demonstrated seizure activity during the course of the study


Secondary Outcome Measures:
  • Extended Glasgow Outcome Score [ Time Frame: at discharge; 3 and 6 months following injury ] [ Designated as safety issue: No ]
    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) [ Time Frame: Discharge; 3 and 6 months following injury ] [ Designated as safety issue: No ]
    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 [ Time Frame: discharge; 3 and 6 months following injury ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: August 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618436

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

No publications provided by University of Cincinnati

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lori Shutter, Director, Neurocritical Care Fellowship Program, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00618436     History of Changes
Other Study ID Numbers: 06-4-6-7
Study First Received: February 8, 2008
Results First Received: August 29, 2013
Last Updated: March 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Cincinnati:
Seizures
Traumatic Brain Injury
Subarachnoid Hemorrhage

Additional relevant MeSH terms:
Hemorrhage
Seizures
Subarachnoid Hemorrhage
Brain Injuries
Wounds and Injuries
Pathologic Processes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Intracranial Hemorrhages
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Craniocerebral Trauma
Trauma, Nervous System
Etiracetam
Phenytoin
Piracetam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014