Clinical trial NCT00727090: Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients
Official title: Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hyponatremia
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma US, Inc.
First posted: 2008-08-01
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Conivaptan (Vaprisol) is FDA-Approved for the treatment of low serum sodium (hyponatremia), but there are few data in patients with neurologic disease. Very low serum sodium in patients with brain injury can be life-threatening and is associated with cerebral edema (swelling of brain tissue). This can be important in patients with brain hemorrhage, brain tumors, or stroke (cerebral infarction).

This is a pilot study to test the hypothesis that conivaptan (Vaprisol) leads to a greater increase in sodium than usual care. Patients will be randomly assigned to usual care or the lower FDA-approved dose of conivaptan (Vaprisol). We will track the use of other interventions, such as the use of hypertonic saline (concentrated salt solution), diuretics and salt tablets. A blinded co-investigator will record neurologic examination results (NIH Stroke Scale and Glasgow Coma Scale).


Eligibility criteria: Inclusion Criteria:

* severe hyponatremia (Na \< 130 mmol/L) or
* symptomatic hyponatremia - Na \< 135 mmol/L for at least six hours with Glasgow Coma Scale \< 15

Exclusion Criteria:

* Enrollment in the NMH high-risk spine protocol. These patients receive large amounts of fluids, have rapid changes in electrolytes, and are typically corrected in 48 hours
* Expected death from any cause
* Known sensitivity or allergy to conivaptan
* Renal failure (baseline creatinine \> 1.5 mg/dL)
* Clinical diagnosis of hypovolemia, or by central venous pressure (CVP) \< 5 mm Hg if a central venous catheter is in place
* Concomitant use of potent inhibitors of cytochrome P-450 isoenzyme 3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir). These agents are not commonly used in the Neuro-ICU
* Clinical diagnosis of liver failure or insufficiency
* Pregnancy (must be excluded before entry)
* Lack of informed consent from the patient or a legally authorized representative (LAR)
* Use of intra-arterial vasodilators (e.g. verapamil, nicardipine) within 24 hours (e.g. for vasospasm after SAH)
* Concern by the Neuro-ICU pharmacist of a drug-drug interaction that would meaningfully impact care (the Neuro-ICU pharmacist will review the medication regimen before recruitment)
* Patients with a diagnosis of diabetes insipidus or treated with vasopressin, since these patients are already treated for abnormal free water balance
* Patients with congestive heart failure, since this is an approved use of the drug (these patients are typically not cared for in the Neuro-ICU)
* Age\<18 years (these patients are not cared for at NMH)
* Inclusion declined by the attending physician or consulting study nephrologist

Primary outcomes:
measure: Change in Serum Sodium From Baseline to 6 Hours
timeFrame: 48 hours
Secondary outcomes:
measure: NIH Stroke Scale
timeFrame: 48 hours
measure: Glasgow Coma Scale
timeFrame: 48 hours
Other outcomes:
measure: Change in Serum Sodium From Baseline to 12 Hours
timeFrame: 12 hours
measure: Change in Serum Sodium From Baseline to 18 Hours
timeFrame: 18 hours
measure: Change in Serum Sodium From Baseline to 24 Hours
timeFrame: 24 hours
measure: Change in Serum Sodium From Baseline to 36 Hours
timeFrame: 36 hours
measure: Change in Serum Sodium From Baseline to 48 Hours
timeFrame: 48 hours
Locations:
Study officials:
affiliation: Northwestern University
name: Andrew M Naidech, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Naidech AM, Paparello J, Liebling SM, Bassin SL, Levasseur K, Alberts MJ, Bernstein RA, Muro K. Use of Conivaptan (Vaprisol) for hyponatremic neuro-ICU patients. Neurocrit Care. 2010 Aug;13(1):57-61. doi: 10.1007/s12028-010-9379-5.