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

Primary Purpose

Traumatic Brain Injury, Subarachnoid Hemorrhage

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Levetiracetam
Phenytoin
Sponsored by
University of Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Seizures, Traumatic Brain Injury, Subarachnoid Hemorrhage

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Cincinnati Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Levetiracetam

Phenytoin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Seizure Incidence
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
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)
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

Full Information

First Posted
February 8, 2008
Last Updated
March 7, 2014
Sponsor
University of Cincinnati
Collaborators
Mayfield Clinic & Spine Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00618436
Brief Title
Assess Safety and Efficacy of Levetiracetam(LEV;Keppra)for Seizure Prevention
Acronym
Keppra
Official Title
Assessment of Seizure Prophylaxis Protocols Using Intravenous Levetiracetam in a Neuroscience Intensive Care Unit
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cincinnati
Collaborators
Mayfield Clinic & Spine Institute

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury, Subarachnoid Hemorrhage
Keywords
Seizures, Traumatic Brain Injury, Subarachnoid Hemorrhage

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levetiracetam
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Phenytoin
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Levetiracetam
Other Intervention Name(s)
Keppra
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Phenytoin
Other Intervention Name(s)
Dilantin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Seizure Incidence
Description
This was the number of patients in each group who demonstrated seizure activity during the course of the study
Time Frame
Duration of study, up to 6 months after the injury
Secondary Outcome Measure Information:
Title
Extended Glasgow Outcome Score
Description
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.
Time Frame
at discharge; 3 and 6 months following injury
Title
Disability Rating Scale (DRS)
Description
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.
Time Frame
Discharge; 3 and 6 months following injury
Title
Incidence of Adverse Events
Time Frame
discharge; 3 and 6 months following injury

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lori Shutter, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Cincinnati Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22342434
Citation
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.
Results Reference
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Assess Safety and Efficacy of Levetiracetam(LEV;Keppra)for Seizure Prevention

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