A multi-center,_double-blind,_pararel-group comparison phase 4 trial to investigate the effect of tolvaptan on mid- to long-term prognosis of heart failure patients

JRCT ID: jRCT1080221581

Registered date:14/09/2011

Basic Information

• Health condition(s) or Problem(s) studied: Volume overload in heart failure that does not respond adequately to other diuretics (e.g., loop diuretics)
• Date of first enrollment: 14/09/2011
• Target sample size: 100
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : tolvaptan
INN of investigational material :
Therapeutic category code : 213 Diuretics
Dosage and Administration for Investigational material : Once-daily oral administration of one tolvaptan 15 mg tablet in the morning

control material(s)
Generic name etc : Placebo
INN of investigational material :
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Once-daily oral administration of one placebo tablet in the morning

Outcome(s)

Primary Outcome

mid- or long-term prognosis

Assessment of events over 26 weeks

Adverse events, serum sodium concentration, clinical laboratory tests, vital signs, 12-lead ECG, M-mode echocardiography, and mortality at Week 26
Change from baseline

Body weight, congenitive findings, cardiothoracic ratio, pulmonary congestion, New York Heart Association (NYHA) Classification, plasma brain natriuretic peptide (BNP) concentration
Change from baseline

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1) Patients from whom informed consent has been properly obtained in writing prior to start of the trial
2) Patients who have been clinically diagnosed with heart failure
3) 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
4) Patients who have been receiving loop diuretics, thiazide diuretics, or anti-aldosterone diuretics
5) Male or female patients of age 20 to 85 years inclusive (at time of informed consent)
6) Patients who, together with their partner(s), are able to use an appropriate method of contraception until 3 months after final trial drug administration
7) Patients who are able to be hospitalized at the trial site for at least 7 days from the start of trial drug administration

Exclude criteria

1) Patients with a history of hypersensitivity to any ingredient of the drug or to tolvaptan analogues (e.g., mozavaptan hydrochloride)
2) Patients with anuria
3) Patients who cannot sense thirst or who have difficulty with fluid intake
4) Patients with hypernatremia (serum sodium concentration > institutional upper limit of normal)
5) Female patients who are pregnant, possibly pregnant, or nursing
6) 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
7) Patients with suspected hypovolemia
8) Patients with an implanted circulatory support device
9) Patients in whom acute cardiac infarction occurred within 30 days prior to the screening examination
10) 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
11) Patients who received tolvaptan within 26 weeks prior to the date of informed consent
12) Patients who are otherwise judged by the investigator or sub-investigator to be inappropriate for inclusion in the trial

Related Information

• Primary Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Secondary ID(s): JapicCTI-111621