Antiepileptic Drugs and Vascular Risk Markers

This study has been terminated.
(study no longer consistent with current clinical practice)
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00774306
First received: October 16, 2008
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Subarachnoid Hemorrhage
Drug: phenytoin
Drug: valproate
Drug: levetiracetam

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Antiepileptic Drugs on Serum Lipids and Inflammation in Patients With Subarachnoid Hemorrhage

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of acute seizures, incidence of late seizures, overall neurologic function (as measured by modified Rankin scale scores) [ Time Frame: 8 weeks, 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: April 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
Drug: phenytoin
Phenytoin is a anti-seizure medication. Participants will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
Other Name: Dilantin, Cerebyx (a phenytoin pro-drug)
Active Comparator: 2
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
Valproate is an anti-seizure medication. Participants will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses.
Other Name: Depakote, Depacon
Active Comparator: 3
Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
Drug: levetiracetam
Levetiracetam is an anti-seizure medication. Participants will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
Other Name: Keppra
No Intervention: 4
Participants randomized to Group 4 will receive no drug intervention.

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00774306

Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Scott Mintzer, MD Assistant Professor of Neurology, Jefferson Comprehensive Epilepsy Center
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00774306     History of Changes
Other Study ID Numbers: K23NS058669, 1K23NS058669
Study First Received: October 16, 2008
Last Updated: June 3, 2014
Health Authority: United States: Federal Government

Keywords provided by Thomas Jefferson University:
vascular risk
lipid fractions
lipoprotein(a)
C-reactive protein
subarachnoid hemorrhage
antiepileptic drug
randomized
seizure
cholesterol

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Etiracetam
Valproic Acid
Anticonvulsants
Phenytoin
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators

ClinicalTrials.gov processed this record on September 18, 2014