Subarachnoid Hemorrhage
Conditions
Keywords
vascular risk, lipid fractions, lipoprotein(a), C-reactive protein, subarachnoid hemorrhage, antiepileptic drug, randomized, seizure, cholesterol
Brief summary
The purpose of this study is to determine if certain seizure medications raise levels of cholesterol and other blood components which could increase the risk of heart attacks and strokes.
Detailed description
There is some evidence that certain seizure medicines may raise levels of cholesterol and other blood components which could increase the risk of heart attacks and strokes, however, more research is needed. Individuals with acute subarachnoid hemorrhage traditionally are treated with seizure medicines, but it is not clear which one is best, or if any such medication is necessary at all. This study is intended to find out if certain seizure medications raise levels of cholesterol and other blood components which could lead to an increased risk of heart attacks and strokes. In this study, 200 people with acute subarachnoid hemorrhage will be randomized to treatment with one of three different seizure medicines-phenytoin, valproate, or levetiracetam-or to receive no seizure medication at all. In each participant, cholesterol and other blood markers that relate to heart attack and stroke risk will be measured shortly after hospital admission and again 8 weeks later. At the 8-week point most participants will have their seizure medication discontinued, and the same blood tests will be repeated. Information from this study could lead to changes in how seizure medications are prescribed both in the subarachnoid hemorrhage population and in other people who are prone to seizures.
Interventions
DRUGphenytoin
Phenytoin is a anti-seizure medication. Participants will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
DRUGvalproate
Valproate is an anti-seizure medication. Participants will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses.
DRUGlevetiracetam
Levetiracetam is an anti-seizure medication. Participants will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Acute subarachnoid hemorrhage, Hunt-Hess Grades I-IV * Within 48 hours of admission
Exclusion criteria
* Grade V subarachnoid hemorrhage * Being treated with a lipid-lowering agent * Contraindication to phenytoin, valproate, or levetiracetam (e.g. history of allergy to one of these agents) * Contraindication to receiving no antiepileptic drug treatment (e.g. history of pre-existing epilepsy, seizure activity on admission EEG)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Serum Cholesterol, Non-HDL Cholesterol, HDL Cholesterol, Lipoprotein(a), and C-reactive Protein From Baseline to Second Draw and Third Draw in Each of the 4 Study Arms | 8 weeks, 16 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores) | 8 weeks, 16 weeks |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phenytoin Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
phenytoin: Phenytoin is a anti-seizure medication. Participants will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses. | 24 |
| Valproate Participants randomized to Group 2 will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses or in a once-daily extended release formulation.
valproate: Valproate is an anti-seizure medication. Participants will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses. | 5 |
| Levetiracetam Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
levetiracetam: Levetiracetam is an anti-seizure medication. Participants will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses. | 16 |
| No Anticonvulsant Participants randomized to Group 4 will receive no drug intervention. | 7 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 6 | 0 | 4 | 5 |
| Overall Study | Protocol Violation | 2 | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Phenytoin | Valproate | Levetiracetam | No Anticonvulsant | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 5 Participants | 14 Participants | 5 Participants | 46 Participants |
| Age, Continuous | 48.5 years | 46 years | 51 years | 49 years | 48 years |
| Region of Enrollment United States | 24 participants | 5 participants | 16 participants | 7 participants | 52 participants |
| Sex: Female, Male Female | 14 Participants | 4 Participants | 10 Participants | 6 Participants | 34 Participants |
| Sex: Female, Male Male | 10 Participants | 1 Participants | 6 Participants | 1 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 1 / 5 | 0 / 16 | 0 / 7 |
| serious Total, serious adverse events | 4 / 24 | 1 / 5 | 4 / 16 | 3 / 7 |
Outcome results
Primary
Change in Serum Cholesterol, Non-HDL Cholesterol, HDL Cholesterol, Lipoprotein(a), and C-reactive Protein From Baseline to Second Draw and Third Draw in Each of the 4 Study Arms
Time frame: 8 weeks, 16 weeks
Secondary
Incidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores)
Time frame: 8 weeks, 16 weeks