A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi- Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF) - VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA)

In order to be eligible for participation in this trial, the subject must:;1. Provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.;2. Be male or female, aged 18 years or older on the day of signing informed consent.;3. Have a history of chronic HF (NYHA class II-IV) on standard therapy before qualifying HF decompensation.;4. Have a previous HF hospitalization within 6 months prior to randomization or IV diuretic treatment for HF (without hospitalization) within 3 months prior to randomization.;5. Have brain natriuretic peptide (BNP) or NT-proBNP levels within 30 days prior to randomization as follows:;NT-proBNP BNP;Sinus Rhythm > or <= 1000 pg/mL > or <= 300 pg/mL;Atrial Fibrillation > or <= 1600 pg/mL > or <= 500 pg/mL;6. Have a left ventricular ejection fraction (LVEF) of <45% assessed within 12 months prior to randomization by any method (most recent measurement must be used to determine eligibility).;7. Meet one of the following criteria:;a) The subject is a male.;b) The subject is a female who is not of reproductive potential, or who is of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug, by complying with acceptable methods of contraception.

The subject must be excluded from participating in the trial if the subject:;1. Is clinically unstable at the time of randomization as defined by:;a. Administration of any intravenous treatment within 24 hours prior to randomization, and/or;b. Systolic blood pressure (SBP) <100 mmHg or symptomatic hypotension.;2. Has concurrent or anticipated use of long-acting nitrates or NO donors including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine.;3. Has concurrent use or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and sildenafil.;4. Has concurrent use or anticipated use of a sGC stimulator such as riociguat.;5. Has known allergy or sensitivity to any sGC stimulator.;6. Is awaiting heart transplantation (United Network for Organ Sharing Class 1A / 1B or equivalent), receiving continuous IV infusion of an inotrope, or has/anticipates receiving an implanted ventricular assist device.;Cardiac Comorbidity;7. Has primary valvular heart disease requiring surgery or intervention, or is within 3 months after valvular surgery or intervention.;8. Has hypertrophic obstructive cardiomyopathy.;9. Has acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy.;10. Has post-heart transplant cardiomyopathy.;11. Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.;12. Has acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction [NSTEMI], or ST elevation myocardial infarction [STEMI]) or coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) within 60 days prior to randomization, or indication for coronary revascularization at time of randomization.;13. Has symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days prior to randomization.;14. Has complex congenital heart disease.;15. Has active endocarditis or constrictive pericarditis.;Non-cardiac comorbidity;16. Has an estimated glomerular filtration rate (eGFR) calculated based on the Modification of Diet in Renal Disease (MDRD) equation <15 mL/min/1.73 m2 or chronic dialysis.;17. Has severe hepatic insufficiency such as with hepatic encephalopathy.;18. Has malignancy or other non-cardiac condition limiting life expectancy to <3 years.;19. Requires continuous home oxygen for severe pulmonary disease.;20. Has current alcohol and/or drug abuse.;21. Has participated in another interventional clinical study and treatment with another investigational product *30 days prior to randomization or plans to participate in any other trial/investigation during the duration of this study.;22. Has a mental or legal incapacitation and is unable to provide informed consent.;23. Has a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the subject*s ability to participate or complete the study.;24. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.;25. Has Interstitial Lung Disease.;26. Is pregnant or breastfeeding or plans to become pregnant or breastfeed during the course of the trial.