Subarachnoid Hemorrhage, Traumatic Brain Injury
Conditions
Keywords
Seizures, Traumatic Brain Injury, Subarachnoid Hemorrhage
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.
Interventions
DRUGLevetiracetam
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.
DRUGPhenytoin
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.
Sponsors
Mayfield Clinic & Spine Institute
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam This group will receive treatment with Levetiracetam. | 34 |
| Phenytoin This group will receive treatment with Phenytoin. | 18 |
| Total | 52 |
Baseline characteristics
| Characteristic | Levetiracetam | Phenytoin | Total |
|---|---|---|---|
| Age, Continuous | 44 years | 35 years | 42.5 years |
| Region of Enrollment United States | 34 participants | 18 participants | 52 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 26 Participants | 13 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 18 |
| serious Total, serious adverse events | 0 / 34 | 0 / 18 |
Outcome results
Primary
Seizure Incidence
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Seizure Incidence | 5 Participants |
| Phenytoin | Seizure Incidence | 3 Participants |
Secondary
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.
Time frame: Discharge; 3 and 6 months following injury
Population: All patients
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Levetiracetam | Disability Rating Scale (DRS) | At Discharge | 24 units on a scale |
| Levetiracetam | Disability Rating Scale (DRS) | At 3 months | 15 units on a scale |
| Levetiracetam | Disability Rating Scale (DRS) | At 6 months | 17 units on a scale |
| Phenytoin | Disability Rating Scale (DRS) | At 6 months | 9 units on a scale |
| Phenytoin | Disability Rating Scale (DRS) | At Discharge | 23 units on a scale |
| Phenytoin | Disability Rating Scale (DRS) | At 3 months | 13 units on a scale |
Secondary
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.
Time frame: at discharge; 3 and 6 months following injury
Population: All patients
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Levetiracetam | Extended Glasgow Outcome Score | At Discharge | 2 units on a scale |
| Levetiracetam | Extended Glasgow Outcome Score | At 3 months | 3 units on a scale |
| Levetiracetam | Extended Glasgow Outcome Score | At 6 months | 3 units on a scale |
| Phenytoin | Extended Glasgow Outcome Score | At Discharge | 2 units on a scale |
| Phenytoin | Extended Glasgow Outcome Score | At 3 months | 3 units on a scale |
| Phenytoin | Extended Glasgow Outcome Score | At 6 months | 3 units on a scale |
Secondary
Incidence of Adverse Events
Time frame: discharge; 3 and 6 months following injury