A Proof-of-concept Trial for OPC 131461 in Patients Hospitalized for Worsening Heart Failure

Inclusion Criteria: * Diagnosis of HF ≥ 3 months prior to screening. * Admitted to the hospital with primary diagnosis of WHF and received treatment with intravenous (IV) diuretics. * Eligible participants will be randomized no earlier than 48 hours and up to 5 days after presentation to the hospital as long as they meet the following definition of stable status: Stable for at least 24 hours, defined by systolic blood pressure (SBP) ≥ 90 millimeters of mercury (mmHg) for preceding 24 hours, no increase in diuretic dose for 24 hours prior to randomization, did not receive IV inotropic or vasodilator (including nitrates) for 24 hours prior to randomization, and no oxygen therapy or mechanical ventilation in the 24 hours prior to randomization * Left ventricular ejection fraction (LVEF) assessed either during hospitalization for Index Event or within 12 months prior to randomization. * Has evidence of incomplete decongestion, indicated by NT-proBNP levels \> 750 picograms per milliliter (pg/mL) (or \> 1000 pg/mL if in atrial fibrillation). At hospital sites where NT proBNP test is unavailable at screening: B-type natriuretic peptide (BNP) \> 375 pg/mL (or \> 500 pg/mL if in atrial fibrillation). Exclusion Criteria: * Primary cause of WHF (Index Event) due to valvular heart disease (defined as severe aortic or primary mitral regurgitation, moderate or severe aortic stenosis, any mitral stenosis requiring surgical repair, or active endocarditis), congenital heart disease, hypertrophic obstructive cardiomyopathy, pulmonary embolism, Type I myocardial infarction, infection, severe anemia, exacerbation of chronic obstructive pulmonary disease (COPD), or sustained ventricular tachycardia, or bradycardia with sustained ventricular rate \< 45 beats/minute. * Duration of hospitalization for Index Event \> 2 weeks at time of screening. * End-stage HF requiring at the time of screening left ventricular assist device (LVAD), intra-aortic balloon pump (IABP) or any similar mechanical support. * Cardiac surgery (coronary artery bypass grafting \[CABG\]), percutaneous coronary intervention (PCI), implantation of a cardiac device or cardiac mechanical support implantation within 30 days prior to randomization or planned during the study * Severely impaired renal function eGFR \< 25 milliliters per minute per 1.73-meter square (mL/min/1.73m\^2). * History of dialysis or kidney transplant. * History of cirrhosis or noncirrhotic portal hypertension. * Severe hyponatremia Sodium (Na) level \< 125 mEq/L (milliequivalents per liter) or hypernatremia Na level \> 145 mEq/L). * Systolic blood pressure \< 90 mmHg at screening. * History of or current hepatitis or acquired immunodeficiency syndrome or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HCV), or human immunodeficiency virus (HIV) antibodies. * History of any significant drug allergy or known or suspected hypersensitivity to any component of the study drug. * Use of any investigational drug within 30 days prior to screening. * History of serious mental disorders that, in the opinion of the investigator, would exclude the participant from participating in this trial. Note: Other protocol-specified inclusion and exclusion criteria may apply.