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

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

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.

Study Overview

• Status: Completed
• Conditions: Severe Traumatic Brain Injury
• Intervention / Treatment: Drug: Conivaptan (Vaprisol)

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Washington

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: June 26, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Estimate): September 10, 2010
• Last Update Submitted That Met QC Criteria: September 8, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Traumatic Brain Injury; Sodium; Conivaptan; Vaprisol
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Conivaptan
• Other Study ID Numbers: 35774-A