Study of the Safety and Efficacy of Conivaptan (Vaprisol®) to Raise Serum Sodium Levels in Patients With Severe Traumatic Brain Injury

NCT00930202 | Completed Phase 1 DMC

• 1 other identifier: 35774-A
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators plan to utilize conivaptan (Vaprisol) to promote isolated water loss, in combination with normal (physiologic) fluid replacement to maintain a normal blood volume status, in patients with severe TBI. The goal of this therapy is to raise blood sodium in a controlled fashion in subjects with severe TBI, and reduce the use of hypertonic saline infusion. We hypothesize that this therapy will maintain a stable state of high blood sodium, while decreasing the overall sodium load needed to achieve these goals.

Conditions

Severe Traumatic Brain Injury

Keywords

Traumatic Brain Injury; Conivaptan; Vaprisol; Sodium

Outcome Measures

Primary Outcomes (1)

• Number of events of excessive rate of increase in sodium levels (>1 mEq/hr).

  Every 4 hours

Secondary Outcomes (5)

• Safety profile: number of events of increased serum sodium levels above the intended target range, and any adverse events occurring during the study period.

  Hospital Stay

• Sodium load: Sodium load is defined as the cumulative amount of sodium administered by enteral and parenteral routes from the time of randomization to 48 hours post-randomization

  Until 48 hours post randomization

• Serum sodium stability: a. Stable state of hypernatremia b. Sodium variability c. Time to achievement of target sodium levels after randomization

  Until 48 hours post randomization

• Fluid balance

  Until 48 hours post randomization

• Cerebral edema: a. Mean ICP in the first 48 hours after randomization b. Reduction of cerebral edema

  Until 48 hours post randomization

Study Arms (2)

Conivaptan (Vaprisol)

EXPERIMENTAL

Conivaptan (Vaprisol) will be administered in a single dose of 20 mg, mixed with 100 mL of 5% dextrose in water, and delivered over 30 minutes.

Drug: Conivaptan (Vaprisol)

Standard Care

NO INTERVENTION

No intervention

Interventions

Conivaptan (Vaprisol) DRUG

Conivaptan (Vaprisol) will be administered in a single dose of 20 mg, mixed with 100 mL of 5% dextrose in water, and delivered over 30 minutes.

Conivaptan (Vaprisol)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old or greater
• Initial diagnosis of an isolated, severe traumatic brain injury (Glasgow Coma Score of 8 or less upon initial evaluation)
• Cerebral edema with a head CT and Marshall classification of diffuse injury type II, III, or IV.
• Primary care team orders to raise blood sodium by 10 mEq/L from baseline.
• Placement of an intraparenchymal fiberoptic monitor to monitor intracranial pressure (ICP).

You may not qualify if:

• Age \< 18 years
• Signs of hypovolemia including systolic BP \< 90 mmHg
• Signs of liver disease including jaundice and ascites
• AST \> 35 units/L
• ALT \> 35 units/L
• Signs of renal disease including history of dialysis
• Serum creatinine \> 1.5 mg/dL
• BUN \> 20 mg/dL range
• Baseline serum sodium \>/= 145 mEq/L
• Pregnant or lactating females
• Concomitant use of digoxin, ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, simvastatin and lovastatin
• Presentation to the tertiary care hospital \> 24 hours post-injury
• Multi-system traumatic injuries
• Diabetes Insipidus
• Anticipation of diagnosis compatible with brain death, or no expectation of survival with 48 hours.

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

conivaptan

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Miriam Treggiari, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 26, 2009
• First Posted: June 30, 2009
• Study Start: August 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: June 1, 2010
• Last Updated: September 10, 2010

Record last verified: 2010-09

Locations

US (1)