Clinical trial NCT01439009: Effect of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients
Official title: A Multi-center,_double-blind,_pararel-group Comparison Trial to Investigate the Effect of Short-term Administration of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients (Phase_4 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Heart failure
Volume overload
Tolvaptan
loop diuretics
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2011-09-22
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Cummulative Incidence of Events at Week 26
timeFrame: Week 26
measure: Mortality （Number of Death）
timeFrame: Week26
measure: Body Weight
timeFrame: Day15
measure: Number of Subjects Whose Lower Limb Edema Severity Grading Improved by One or More Grade
timeFrame: Day15
measure: Jugular Venous Distension
timeFrame: Day15
measure: Change in Liver Size From Baseline
timeFrame: Day15
measure: Pulmonary Rales
timeFrame: Day15
measure: Third Heart Sound
timeFrame: Day15
measure: Cardiothoracic Ratio
timeFrame: Day15
measure: Pulmonary Congestion
timeFrame: Day15
measure: Plasma Brain Natriuretic Peptide (BNP) Concentration
timeFrame: Day15
measure: Dypnea
timeFrame: Day15
measure: Number of Subjects Whose New York Heart Association (NYHA) Classification Improved by One More Grade From Baseline
timeFrame: The day after last IMP administration and Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Chube Region
country: Japan
city: Chushikoku Region
country: Japan
city: Hokkaido Region
country: Japan
city: Hokuriku Region
country: Japan
city: Kansai Region
country: Japan
city: Kanto Region
country: Japan
city: Kyushu Region
country: Japan
city: Tohoku Region
country: Japan
Study officials:
References: