Effect of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Tolvaptan; Placebo of tolvaptan
Intervention description: Once-daily oral administration of one tolvaptan 15 mg tablet in the morning; Once-daily oral administration of one placebo tablet in the morning
Intervention MeSH terms: Tolvaptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 100.0
Sex: All
Minimum age: 20 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Heart failure; Volume overload; Tolvaptan; loop diuretics

Summary:

      One tolvaptan 15 mg tablet or placebo tablet will be orally administered once daily in the
      morning for up to 14 days to heart failure patients with volume overload that does not show
      adequate response to other diuretics such as loop diuretics in order to investigate the
      effect of tolvaptan on the mid- to long-term prognosis of the target population. The efficacy
      of tolvaptan during the treatment period will also be investigated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients from whom informed consent has been properly obtained in writing prior to
             start of the trial

          -  Patients who have been clinically diagnosed with heart failure

          -  Patients with any of the following conditions or symptoms: lower limb edema, dyspnea,
             jugular venous distension, hepatomegaly, pulmonary rales, third heart sound, or
             pulmonary congestion

          -  Patients who have been receiving loop diuretics, thiazide diuretics, or
             anti-aldosterone diuretics

          -  Male or female patients of age 20 to 85 years inclusive (at time of informed consent)

          -  Patients who, together with their partner(s), are able to use an appropriate method of
             contraception until 3 months after final trial drug administration

          -  Patients who are able to be hospitalized at the trial site for at least 7 days from
             the start of trial drug administration

        Exclusion Criteria:

          -  Patients with a history of hypersensitivity to any ingredient of the drug or to
             tolvaptan analogues (e.g., mozavaptan hydrochloride)

          -  Patients with anuria

          -  Patients who cannot sense thirst or who have difficulty with fluid intake

          -  Patients with hypernatremia (serum sodium concentration > institutional upper limit of
             normal) 5) Female patients who are pregnant, possibly pregnant, or nursing

          -  Patients judged by the investigator or subinvestigator to be inappropriate for
             inclusion in the trial due to any of the following conditions or symptoms:

               -  Hyponatremia (serum sodium concentration < 125 mEq/L)

               -  Serious coronary artery disease or cerebrovascular disease

               -  Hyperkalemia

               -  Severe renal disorder

               -  Poorly controlled diabetes mellitus

               -  Severe hepatic disease

               -  Impaired urinary excretion due to urinary stenosis, calculus, or tumor

               -  Cardiac valve disease with significant heart valve stenosis

               -  Malignant tumor of unfavorable prognosis

          -  Patients with suspected hypovolemia

          -  Patients with an implanted circulatory support device

          -  Patients in whom acute cardiac infarction occurred within 30 days prior to the
             screening examination

          -  Patients who participated in any other clinical trial or postmarketing clinical trial
             within 30 days prior to the date of informed consent for the present trial

          -  Patients who received tolvaptan within 26 weeks prior to the date of informed consent

          -  Patients who are otherwise judged by the investigator or sub-investigator to be
             inappropriate for inclusion in the trial