heart failure
Conditions
Interventions
Group 1: MK-1242 (vericiguat) uptitrated from 2.5 mg to 5 mg to 10mg once
daily, on a background of standard of care
Group 2: placebo once daily, on a background of standard of care
Heart failure
Vericiguat
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time-to first occurrence of the composite of CV death or HF hospitalization | — |
Secondary
| Measure | Time frame |
|---|---|
| - Time to CV death - Time to first HF hospitalization * Time to total HF hospitalizations (first and recurrent) * Time to first occurrence of the composite of all-cause mortality or HF hospitalization * Time to all-cause mortality | — |
Countries
Austria, Belgium, Bulgaria, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed