Traumatic Brain InjuryPhase 4KeppraNCT00618436
Assess Safety and Efficacy of Levetiracetam(LEV;Keppra)for Seizure Prevention
A Phase 4 study testing Levetiracetam and Phenytoin in people with Traumatic Brain Injury and Subarachnoid Hemorrhage, run by University of Cincinnati at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury, Subarachnoid Hemorrhage
- What is being tested?
- Levetiracetam and Phenytoin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Sep 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Cincinnati Hospital
Cincinnati, Ohio, 45220
About this study
Official title: 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.
Read the 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.
- Conditions
- Traumatic Brain Injury, Subarachnoid Hemorrhage
- Being tested
- Levetiracetam, Phenytoin
- Keywords
- Seizures, Traumatic Brain Injury, Subarachnoid Hemorrhage
- Medical subject headings
- Brain Injuries, Traumatic, Subarachnoid Hemorrhage, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevetiracetamDrug
Also called Keppra
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.
PhenytoinDrug
Also called Dilantin
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.
| Study group | Role | What they receive |
|---|---|---|
| Levetiracetam | Active comparator | 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. Receives: Drug: Levetiracetam |
| Phenytoin | Active comparator | 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. Receives: Drug: Phenytoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seizure Incidence
This was the number of patients in each group who demonstrated seizure activity during the course of the study
Measured: Duration of study, up to 6 months after the injury
Secondary outcomes (3)
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.
Measured: 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.
Measured: Discharge; 3 and 6 months following injury
Incidence of Adverse Events
Measured: discharge; 3 and 6 months following injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2008 (estimated)
- Study startAug 2007
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Mayfield Clinic & Spine Institute
- Responsible party
- Principal investigator, Lori Shutter, University of Pittsburgh
- Investigators
- Lori Shutter, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00618436
- Sponsor's protocol ID
- 06-4-6-7
- Acronym
- Keppra
- Status last verified
- Mar 2014
- First submitted
- 8 Feb 2008
- Last updated
- 7 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 22342434
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Seizure Prophylaxis Protocols Using Intravenous Levetiracetam in a Neuroscience Intensive Care Unit
- ClinicalTrials.gov ID
- NCT00618436
- Acronym / sponsor ID
- Keppra / 06-4-6-7
- Conditions
- Traumatic Brain Injury, Subarachnoid Hemorrhage
- Keywords
- Seizures, Traumatic Brain Injury, Subarachnoid Hemorrhage
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Mayfield Clinic & Spine Institute
- Study start
- Aug 2007
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 20 Feb 2008 (estimated)
- Results
- Posted 7 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam | Active comparator | Drug: LevetiracetamGroup 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. |
| Phenytoin | Active comparator | Drug: PhenytoinGroup 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevetiracetamAlso: KeppraLevetiracetam 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. | Drug | Levetiracetam |
| PhenytoinAlso: DilantinThe 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. | Drug | Phenytoin |
Primary outcome
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
3 secondary outcomes
Extended Glasgow Outcome Score
Time frame: at discharge; 3 and 6 months following injury
Disability Rating Scale (DRS)
Time frame: Discharge; 3 and 6 months following injury
Incidence of Adverse Events
Time frame: discharge; 3 and 6 months following injury
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22342434Steinbaugh 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lori Shutter, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levetiracetam and Phenytoin in people with Traumatic Brain Injury and Subarachnoid Hemorrhage, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seizure Incidence (time frame: Duration of study, up to 6 months after the injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00618436, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2014.