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

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT00930202

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Traumatic Brain Injury	Drug: Conivaptan (Vaprisol)	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2009

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Conivaptan (Vaprisol) 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) 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.
No Intervention: Standard Care No intervention

Arm

Intervention/Treatment

Experimental: Conivaptan (Vaprisol)

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)

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.

No Intervention: Standard Care

No intervention

Outcome Measures

Primary Outcome Measures

Number of events of excessive rate of increase in sodium levels (>1 mEq/hr). [Every 4 hours]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 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).

Exclusion Criteria:

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.