Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients
Condition: Hyponatremia
MeSH terms: Hyponatremia
Intervention: Conivaptan
Intervention description: Conivaptan 20 mg once, followed by conivaptan 20 mg over 24 hours
Intervention MeSH terms: Conivaptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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