Phase III Double Blind Trial of Valproate Sodium for Prophylaxis of Post Traumatic Seizures - Full Text View

Purpose

OBJECTIVES: I. Determine whether treating head injured patients with valproate sodium will reduce the risk of developing seizures as a result of the head injury.

II. Determine the safety of valproate, the appropriate dose, and the effect valproate may have on the recovery of the brain's ability to compute numbers, solve problems, remember information, and control the movement of limbs after head injury.

Condition	Intervention	Phase
Post-Traumatic Seizure Disorder Head Injuries	Drug: phenytoin Drug: valproate sodium	Phase III

Genetics Home Reference related topics:

pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy

MedlinePlus related topics:

Epilepsy Seizures Traumatic Brain Injury

Drug Information available for:

Divalproex sodium Valproate Sodium Valproic acid Phenytoin Phenytoin sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	385
Study Start Date:	February 1991

Detailed Description:

PROTOCOL OUTLINE: This is a randomized, double blind trial involving 3 treatment groups.

On day 1, controls receive phenytoin IV over 1 hour. On days 2 through 7, controls receive 2 doses each of phenytoin and placebo daily, intravenously. From day 8 through 6 months, controls receive placebo IV 4 times daily, then placebo tablets are administered.

On day 1, the experimental group receives a loading dose of valproate sodium intravenously over 1 hour within 24 hours of injury. Then, patients are divided into 2 subgroups.

From day 2 through 1 month, one group of patients receives valproate IV 4 times daily over 1 hour until tablets are tolerated. Patients receive placebo tablets by mouth 4 times daily from month 2 through month 6.

On day 2, the other group of patients receives valproate IV 4 times daily and continues for 6 months until tablets (same dose) are tolerated.

If patients remain seizure free between day 8 and 6 months, the number of valproate or placebo tablets are tapered over 1 week.

Each patient receives a full neuropsychological and psychosocial examination at 1, 6, and 12 months after injury.

Untreated observation of patients continues until 2 years after injury.

Eligibility

Ages Eligible for Study:	14 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Any patient developing the following conditions within 24 hour postinjury:

Cortical contusion
Depressed skull fracture
Subdural hematoma
Epidural hematoma
Intracerebral hematoma
Penetrating head wound
Seizures occurring subsequent to head injury

--Prior/Concurrent Therapy--

No antiseizure medication prior to injury or between the injury and study drug loading
Surgery: No prior neurosurgical operation for which the skull and dura mater were opened

--Patient Characteristics--

Age: 14 and over
Hematopoietic: No abnormal coagulation profile
Hepatic: No history of chronic or alcoholic liver disease Adequate liver function as indicated by ALT less than 1.5 times the upper limit of normal
Other: Not pregnant No injuries greater than 24 hours old No history of seizures prior to injury No prior history of significant head injury or neurological condition requiring medical attention

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004817

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Harborview Injury Prevention and Research Center

Investigators


Study Chair:	H. Richard Winn	Harborview Injury Prevention and Research Center

More Information

Study ID Numbers:	199/12249, UW-19643
First Received:	February 24, 2000
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00004817
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

neurologic and psychiatric disorders

rare disease

seizures

Study placed in the following topic categories:

Craniocerebral Trauma

Post-traumatic epilepsy

Seizures

Rare Diseases

Wounds and Injuries

Central Nervous System Diseases

Disorders of Environmental Origin

Trauma, Nervous System

Epilepsy, Post-Traumatic

Brain Diseases

Valproic Acid

Phenytoin

Signs and Symptoms

Epilepsy

Mental Disorders

Neurologic Manifestations

Brain Injuries

Additional relevant MeSH terms:

Neurotransmitter Agents

Tranquilizing Agents

Molecular Mechanisms of Pharmacological Action

Nervous System Diseases

Physiological Effects of Drugs

Psychotropic Drugs

Central Nervous System Depressants

Enzyme Inhibitors

Antimanic Agents

Pharmacologic Actions

Therapeutic Uses

GABA Agents

Central Nervous System Agents

Anticonvulsants

ClinicalTrials.gov processed this record on December 03, 2008

Sponsors and Collaborators:	National Institute of Neurological Disorders and Stroke (NINDS) Harborview Injury Prevention and Research Center
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00004817