Pilot Study of Using Copeptin to Predict Response to Tolvaptan
Condition: Cardiovascular Diseases; Heart Diseases; Heart Failure
MeSH terms: Diabetes Insipidus; Heart Failure; Cardiovascular Diseases; Heart Diseases
Intervention: tolvaptan
Intervention description: oral, 30 mg, single dose, one time administration
Intervention MeSH terms: Tolvaptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: tolvaptan; copeptin; heart failure; vasopressin antagonist

Summary:

      This pilot study will investigate the association between levels of the peptide copeptin and
      response to tolvaptan, a drug that blocks the action of the water retaining hormone
      vasopressin. The study will enroll stable outpatients with CHF with reduced LVEF (≤45)
      selected by targeting upper and lower quartile copeptin levels at screening (10 each). The
      treatment phase of the study will be a prospective, single-arm, open label protocol. All
      patients will receive active therapy consisting of a single oral dose of 30 mg of tolvaptan
      with body weight, fluid intake, and urine output monitored in a research unit for 24 hours.

      For analysis of study endpoints, patients in the single intervention arm will be stratified
      by a prospectively determined cut-point of copeptin level into two groups (≥10 versus <10
      pmol/L). The copeptin level used for the two group stratification will be the blinded
      copeptin value obtained at baseline from the hospital phase prior to administration of
      tolvaptan.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female patients with a history of chronic symptomatic heart failure, defined
             as dyspnea on exertion or edema, due to cardiac dysfunction, of at least one month's
             duration

          2. Left ventricular ejection fraction ≤ 45% as documented by quantitative assessment by
             an accepted imaging technique within one year of screening

          3. Meet baseline copeptin criteria for entry

          4. Currently taking a diuretic (with diuretic defined as any loop or thiazide diuretic or
             aldosterone antagonist at any dose)

        Exclusion Criteria:

          1. Current New York Heart Association Functional Class IV heart failure

          2. Patients who are felt to be volume depleted based on clinical examination or need to
             reduce diuretic administration

          3. Presence of clinical contraindications to tolvaptan

          4. Episode of acute myocardial infarction or acute coronary syndrome within the past 3
             months

          5. Cardiovascular surgical procedure within the past 4 weeks

          6. CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid
             cardiomyopathy.

          7. History of primary significant liver disease or acute hepatic failure, as defined by
             the investigator.

          8. Chronic uncontrolled diabetes mellitus as determined by the investigator.

          9. Supine systolic arterial blood pressure < 90 mmHg at screening

         10. Serum creatinine > 3.5 mg/dL at screening

         11. Serum potassium > 5.5 mEq/L or < 3.5 mEq/L at screening

         12. Subjects currently treated with hemofiltration or dialysis

        j. Subjects judged by the investigator to be unable to maintain accurate intake and output
        during their hospitalization related to medical or other problems