Intracranial Aneurysms, Seizure
Conditions
Brief summary
After a thorough review of the existing literature as well as a review of our own practice, the investigators have concluded that the decision to treat patients undergoing aneurysm repair with levetiracetam has reached true clinical equipoise. In other words, the investigators cannot favor a decision to either administer or not administer this drug in these patients based on the existing information. The utility of anti-epileptic prophlaxis in the perioperative period for patients undergoing intracranial aneurysm repair remains a common practice that is not supported by the current literature that includes retrospective analyses as well as prospective trials for similar but not identical types of patients. The investigators propose to settle this dilemma by performing a prospective randomized trial in patients undergoing aneurysm repair in order to definitively determine if the common practice of perioperative antiepileptic drug administration has any utility. The study will be extended to June 2024 to allow for a 5 year follow up of the last enrolled patient in June, 2019.
Interventions
DRUGLevetiracetam
Details covered in Arm Descriptions.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (≥18 years) * Presence of intracranial aneurysm (with or without rupture) * Treating surgeon has recommended surgical repair of the aneurysm
Exclusion criteria
* History of seizures within last 10 years * History of epilepsy * History of prior stroke * Currently prescribed medication with anti-epileptic activity (keppra, dilantin, tegretol, lamictal, topamax, etc.) * Brain tumor * Pregnant or nursing woman * Known levetiracetam allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Seizure | 5 years from procedure | Incidence of seizure reported as number of participants who had at least one seizure within the relevant date range. Data collected at hospital discharge, 1-2 months, 4-6 months, 6-12 months, and 5 years. Data is not cumulative. Counts reflect the number of participants who experienced a seizure since their previous check-in. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Seizure | To compare duration of seizure in each randomization group | Duration of seizure |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam 500 mg intravenous dose during the operative case then 500 mg orally twice a day for a total of seven days.
Levetiracetam: Details covered in Arm Descriptions. | 40 |
| No Levetiracetam No levetiracetam during the operative phase. | 42 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 8 |
| Overall Study | Lost to Follow-up | 17 | 14 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | No Levetiracetam | Total | Levetiracetam |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 17 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 65 Participants | 31 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 42 Participants | 82 Participants | 40 Participants |
| Sex: Female, Male Female | 30 Participants | 57 Participants | 27 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 40 | 8 / 42 |
| other Total, other adverse events | 7 / 40 | 3 / 42 |
| serious Total, serious adverse events | 2 / 40 | 2 / 42 |
Outcome results
Primary
Incidence of Seizure
Incidence of seizure reported as number of participants who had at least one seizure within the relevant date range. Data collected at hospital discharge, 1-2 months, 4-6 months, 6-12 months, and 5 years. Data is not cumulative. Counts reflect the number of participants who experienced a seizure since their previous check-in.
Time frame: 5 years from procedure
Population: The number of participants analyzed differs from the totals enrolled as some subjects withdrew consent after randomization or were taken out of the study due to physician decision.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levetiracetam | Incidence of Seizure | Hospitalization | 2 Participants |
| Levetiracetam | Incidence of Seizure | 1-2 Months | 0 Participants |
| Levetiracetam | Incidence of Seizure | 4-6 Months | 0 Participants |
| Levetiracetam | Incidence of Seizure | 6-12 Months | 0 Participants |
| Levetiracetam | Incidence of Seizure | 5 years | 1 Participants |
| No Levetiracetam | Incidence of Seizure | 5 years | 2 Participants |
| No Levetiracetam | Incidence of Seizure | 6-12 Months | 0 Participants |
| No Levetiracetam | Incidence of Seizure | 1-2 Months | 0 Participants |
| No Levetiracetam | Incidence of Seizure | Hospitalization | 1 Participants |
| No Levetiracetam | Incidence of Seizure | 4-6 Months | 0 Participants |
Secondary
Duration of Seizure
Duration of seizure
Time frame: To compare duration of seizure in each randomization group
Population: While this was originally intended to be a measure collected for this study, the unpredictability of seizure occurrences and the consequent challenges with observing them consistently resulted in our being unable to collect this data from participants.