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

Study Overview
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Brief Summary
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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.

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

Conditions
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Severe Traumatic Brain Injury

Intervention / Treatment
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* Drug: Conivaptan (Vaprisol)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conivaptan (Vaprisol)<br>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)<br>* 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.<br>|
| No Intervention: Standard Care<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic Brain Injury, Conivaptan, Vaprisol, Sodium