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

Severe Traumatic Brain Injury Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00930202
• Other study ID #: 35774-A
• Status: Completed
• Phase: Phase 1
• First received: June 26, 2009
• Last updated: September 8, 2010
• Start date: August 2009
• Est. completion date: June 2010

Study information

• Verified date: September 2010
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Severe Traumatic Brain Injury

Intervention

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.

Locations

Country	Name	City	State
United States	Harborview Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of events of excessive rate of increase in sodium levels (>1 mEq/hr).		Every 4 hours	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	Yes
Secondary	Fluid balance		Until 48 hours post randomization	No
Secondary	Cerebral edema: a. Mean ICP in the first 48 hours after randomization b. Reduction of cerebral edema		Until 48 hours post randomization	Yes