Clinical trial NCT00930202: Study of the Safety and Efficacy of Conivaptan (Vaprisol®) to Raise Serum Sodium Levels in Patients With Severe Traumatic Brain Injury
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Severe Traumatic Brain Injury
Keywords: Traumatic Brain Injury
Conivaptan
Vaprisol
Sodium
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2009-06-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of events of excessive rate of increase in sodium levels (>1 mEq/hr).
timeFrame: Every 4 hours
Secondary outcomes:
measure: Safety profile: number of events of increased serum sodium levels above the intended target range, and any adverse events occurring during the study period.
timeFrame: Hospital Stay
measure: 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
timeFrame: Until 48 hours post randomization
measure: Serum sodium stability: a. Stable state of hypernatremia b. Sodium variability c. Time to achievement of target sodium levels after randomization
timeFrame: Until 48 hours post randomization
measure: Fluid balance
timeFrame: Until 48 hours post randomization
measure: Cerebral edema: a. Mean ICP in the first 48 hours after randomization b. Reduction of cerebral edema
timeFrame: Until 48 hours post randomization
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: Miriam Treggiari, MD
role: PRINCIPAL_INVESTIGATOR
References: