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

Phase 1

Completed

• Conditions: Severe Traumatic Brain Injury
• Interventions: Drug: Conivaptan (Vaprisol)

• Registration Number: NCT00930202
• Lead Sponsor: University of Washington

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-06-26
• Study First Submitted QC: 2009-06-29
• Study First Posted: 2009-06-30
• Study Start: 2009-08
• Primary Completion: 2010-05
• Study Completion: 2010-06
• Status Verified: 2010-09
• Last Update Submitted: 2010-09-08
• Last Update Posted: 2010-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conivaptan (Vaprisol)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Harborview Medical Center; 🇺🇸 Seattle, Washington, United States