Antiepileptic Drugs and Vascular Risk Markers

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effects of Antiepileptic Drugs on Serum Lipids and Inflammation in Patients With Subarachnoid Hemorrhage

Conditions
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Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: phenytoin
* Drug: valproate
* Drug: levetiracetam


Participation Criteria
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Eligibility Criteria
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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)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses. | Drug: phenytoin<br>* Phenytoin is a anti-seizure medication. Participants will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.<br>* Other names: Dilantin, Cerebyx (a phenytoin pro-drug);|
| Active Comparator: 2<br>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. | Drug: valproate<br>* Valproate is an anti-seizure medication. Participants will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses.<br>* Other names: Depakote, Depacon;|
| Active Comparator: 3<br>Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses. | Drug: levetiracetam<br>* Levetiracetam is an anti-seizure medication. Participants will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.<br>* Other names: Keppra;|
| No Intervention: 4<br>Participants randomized to Group 4 will receive no drug intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores) |  | 8 weeks, 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vascular risk, lipid fractions, lipoprotein(a), C-reactive protein, subarachnoid hemorrhage, antiepileptic drug, randomized, seizure, cholesterol