Tolvaptan to Reduce Length of Stay in Hospitalized Patients With Cirrhosis and Hyponatremia
Condition: Hyponatremia
MeSH terms: Hyponatremia
Intervention: Tolvaptan; Placebo; Hepatic Encephalopathy Assessment; Quality of Life Assessment; Vital signs; Blood laboratory tests; Ascites Evaluation; Edema
Intervention description: 15 mg once daily; 15 mg once daily; The Number connection test, Digit symbol test, Constructional apraxia, Inhibitory control test, Repeatable Battery for the Assessment of Neuropsychological Status will be administered on Days 1, 2, 4, 6, and 8; discharge day; Weeks 1-4 post-discharge; and Months 2-6 post-discharge.; The SF-36 and Liver Disease Questionnaire will be administered on Day 1, Discharge day, Weeks 1-4 post-discharge, and months 2-6 post-discharge; Vital signs (blood pressure, heart rate, respiration, temperature, weight, height) will be recorded at every visit.; Blood laboratory tests (chemistry, hematology, liver function, urine electrolytes, renin, and copeptin) will be recorded at every visit.; Ascites will be assessed at every visit.; Edema will be assessed at every visit.
Intervention MeSH terms: Tolvaptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hyponatremia; Dilutional Hyponatremia; Euvolemic Hyponatremia; Hypervolemic Hyponatremia; Fluid Restriction; Tolvaptan

Summary:

      Hyponatremia is a condition in which there is a low sodium level in the blood. Individuals
      with cirrhosis may develop low blood sodium as a complication of their liver disease. In
      these patients, the presence of low blood sodium may exacerbate other complications such as
      encephalopathy, resulting in confusion, drowsiness, or coma. It may also affect the ability
      of the body to fight infection. In certain cases, cirrhotic patients may be hospitalized for
      the treatment of their low blood sodium.

      The drug tolvaptan is currently FDA approved for the treatment of hyponatremia in patients
      with cirrhosis. Although it has been shown to increase the sodium level, the clinical trials
      that led to its approval did not otherwise assess clinical benefit of the drug.

      This study is designed to determine whether patients with cirrhosis derive a clinical benefit
      when they receive tolvaptan for the treatment of hyponatremia within 2 days of admission.
      Specifically, whether it is associated with shortened length of stay and improvement in other
      complications of cirrhosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cirrhosis

          -  Screening within 24 hours of admission

          -  Na level less than 130mEq/L

          -  Presence of fluid overload with either history of ascites or edema

          -  Cr < 2.0mg/dl

          -  Planned length of stay after randomization of at least 24 hours

          -  Anticipated survival of at least 8 days

          -  Ability to provide informed consent

        Exclusion Criteria:

          -  Hospitalization greater than 24 hours at screening

          -  Depletional hyponatremia

          -  Hyponatremia due to hyperglycemia

          -  Acute and transient hyponatremia associated with head trauma or post-operative states

          -  Hyponatremia due to primary polydipsia, adrenal insufficiency, or hypothyroidism

          -  Urgent need for treatment of hyponatremia with saline or hypertonic saline

          -  Treatment with demeclocycline, lithium chloride, and urea

          -  Cr greater than 2.0mg/dl

          -  Stage 3 or 4 hepatic encephalopathy

          -  Inability to provide informed consent

          -  Planned discharge within 24 hours

          -  Anticipated survival less than 8 days

          -  GI bleeding within one month of enrollment