Antiepileptic Drugs and Vascular Risk Markers

Not Applicable

Terminated

• Conditions: Subarachnoid Hemorrhage
• Interventions: Drug: phenytoin; Drug: levetiracetam; Drug: valproate

• Registration Number: NCT00774306
• Lead Sponsor: Thomas Jefferson University

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.

Study Timeline

• Study First Submitted: 2008-10-16
• Study First Submitted QC: 2008-10-16
• Study First Posted: 2008-10-17
• Study Start: 2009-04
• Primary Completion: 2012-06
• Study Completion: 2012-06
• Results First Submitted: 2014-11-19
• Results First Submitted QC: 2014-11-19
• Results First Posted: 2014-11-25
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-14
• Last Update Posted: 2017-12-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 52

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	phenytoin	Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
3	levetiracetam	Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
2	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Incidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores)	8 weeks, 16 weeks