Efficacy and Safety Trial of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure

Phase 3

Completed

Conditions: Congestive Heart Failure

Interventions: Drug: OPC-61815
Drug: Tolvaptan Tab 15 MG

Registration Number: NCT03772041

Lead Sponsor: Otsuka Pharmaceutical Co., Ltd.

Brief Summary: To confirm the non-inferiority of OPC-61815 16-mg injection to tolvaptan 15-mg tablet using as the primary endpoint the change in body weight following 5-day intravenous administration of OPC-61815 16-mg injection or 5-day oral administration of tolvaptan 15-mg tablet to CHF patients with volume overload despite having received diuretics other than vasopressin antagonists

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 294

Inclusion Criteria

Patients who are currently on treatment with any of the following diuretics
1. Loop diuretics equivalent to furosemide tablet or fine granules at a dose of 40 mg/day or higher
2. Concomitant use of a loop diuretic and a thiazide diuretic (including thiazide analogs) at any dose
3. Concomitant use of a loop diuretic and an aldosterone antagonist or potassium-sparing diuretic agent at any dose
Patients with congestive heart failure in whom lower limb edema, pulmonary congestion, and/or jugular venous distension due to volume overload is present
Patients who are currently hospitalized or who are able to be hospitalized during the trial

Exclusion Criteria

Patients with acute heart failure
Patients who are on a ventricular assist device
Patients who are unable to sense thirst or who have difficulty with fluid intake

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OPC-61815 injection 16 mg	OPC-61815	Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg
Tolvaptan tablet 15mg	Tolvaptan Tab 15 MG	Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Body Weight	Baseline, Day 6	Change in body weight from baseline (before investigational medicinal product \[IMP\] administration on Day 1) at time of final IMP administration (day after final IMP administration). A negative change from baseline indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Jugular Venous Distension and Hepatomegaly	Baseline, Day 6	* Jugular Venous Distension: the presence of Jugular Venous Distension was checked, and if present, the height (in cm) from the sternal angle to the highest point of pulsation in the internal Jugular vein was measured with the subject in a semi-upright position. A negative change from baseline indicates improvement. * Hepatomegaly: the presence of a palpable liver was checked, and if present, the width (distance from the right costal arch of the right chest, in cm) was measured. A negative change from baseline indicates improvement.
Improvement Rate for Lower Limb Edema and Pulmonary Congestion	Baseline, Day 6	The improvement rate was defined as the percentage of subjects in whom the symptom was present at baseline and it markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated
Percentage of Subjects Who Achieve Resolution of Pulmonary Rales and Third Cardiac Sound	Baseline, Day 6	Percentage of subjects in whom the symptom was present at baseline and disappeared after IMP administration was provided. * The presence of pulmonary rales was checked by auscultation. * The presence of cardiac third sound was checked by auscultation.
Improvement Rate for New York Heart Association (NYHA) Classification	Baseline, Day 6	NYHA classification assesses the severity of heart failure based on subjective symptoms as follows. Class I: No limitations of physical activity. Ordinary physical activity caused no undue fatigue, palpitation, dyspnea or anginal pain. Class II: Slight limitation of physical activity, comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea or anginal pain. Class III: Marked limitation of physical activity, comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea or anginal pain. Class IV: Inability to carry on any physical activity without discomfort. heart failure or anginal syndrome may have been present even at rest. If any physical activity was undertaken, discomfort was increased. Of the subjects with Class II or higher at baseline, the percentage of subjects whose NYHA classification stage at the time of final IMP administration improved by 1 or more grades was provided.