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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conivaptan (Vaprisol) | Experimental | 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. |
|
| Standard Care | No Intervention | No intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Conivaptan (Vaprisol) | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of events of excessive rate of increase in sodium levels (>1 mEq/hr). | Every 4 hours |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Age < 18 years
Signs of hypovolemia including systolic BP < 90 mmHg
Signs of liver disease including jaundice and ascites
Signs of renal disease including history of dialysis
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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| Name | Affiliation | Role |
|---|---|---|
| Miriam Treggiari, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
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| 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 |
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| C106389 | conivaptan |
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