Antiepileptic Drugs and Vascular Risk Markers

Thomas Jefferson University

Status: Terminated

Conditions: Subarachnoid Hemorrhage

Treatments: Drug: levetiracetam; Drug: valproate; Drug: phenytoin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00774306

1K23NS058669 (U.S. NIH Grant/Contract)

K23NS058669

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 4 patient groups

1

Active Comparator group

Description:

Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.

Treatment:

Drug: phenytoin

2

Active Comparator group

Description:

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.

Treatment:

Drug: valproate

3

Active Comparator group

Description:

Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.

Treatment:

Drug: levetiracetam

4

No Intervention group

Description:

Participants randomized to Group 4 will receive no drug intervention.