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

University of Washington

Status and phase: Completed; Phase 1

Conditions: Severe Traumatic Brain Injury

Treatments: Drug: Conivaptan (Vaprisol)

Study type: Interventional

Funder types: Other

Identifiers

NCT00930202

35774-A

Details and patient eligibility

About

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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

Conivaptan (Vaprisol)

Experimental group

Description:

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.

Treatment:

Drug: Conivaptan (Vaprisol)

Standard Care

No Intervention group

Description:

No intervention