Phase III Double Blind Trial of Valproate Sodium for Prophylaxis of Post Traumatic Seizures

NCT ID: NCT00004817

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 385 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1991-02-28

Brief Summary

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.

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.

Conditions

Post-Traumatic Seizure Disorder; Head Injuries

Keywords

neurologic and psychiatric disorders; rare disease; seizures

Study Design

• Primary Study Purpose: TREATMENT

Interventions

phenytoin

Intervention Type: DRUG

valproate sodium

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Harborview Injury Prevention and Research Center

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: lead

Principal Investigators

H. Richard Winn

Role: STUDY_CHAIR

Harborview Injury Prevention and Research Center

Other Identifiers

UW-19643

Identifier Type: -

Identifier Source: secondary_id

199/12249

Identifier Type: -

Identifier Source: org_study_id