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

Head Injuries Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004817
• Other study ID #: 199/12249
• Secondary ID: UW-19643
• Status: Completed
• Phase: Phase 3
• First received: February 24, 2000
• Last updated: June 23, 2005
• Start date: February 1991

Study information

• Verified date: December 2001
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 385
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy
• Epilepsy, Post-Traumatic
• Head Injuries
• Post-Traumatic Seizure Disorder
• Seizures

Intervention

Drug:
• phenytoin

• valproate sodium

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)	Harborview Injury Prevention and Research Center