Treatment of chronic heart failure with reduced ejection fraction (HFrEF) MedDRA version: 20.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: Vericiguat
Product Code: MK-1242
BAY1021189
Pharmaceutical Form: Tablet
INN or Proposed INN: Vericiguat
CAS Number: 1350653-20-1
Current Sponsor code: MK-1242
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
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 = 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 =65 years) yes F.1.3.1 Number of subjects for this age range 872
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. Note: Subjects with a known history of hypersensitivity to the active substance of the investigational product or to any of its constituents will be excluded from the trial. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of the oral soluble guanylate cyclase (sGC) stimulator MK-1242 (vericiguat) in comparison to placebo on a background of standard of care in increasing the time to first occurrence of the composite of CV death or HF hospitalization in subjects with HFrEF.;Secondary Objective: In subjects with HFrEF on a background of standard of care: (1) To evaluate the efficacy of MK-1242 (vericiguat) in increasing the time to CV death in comparison to placebo. (2) To evaluate the efficacy of MK-1242 (vericiguat) in increasing the time to first HF hospitalization in comparison to placebo. (3) To evaluate the efficacy of MK-1242 (vericiguat) in increasing the time to total HF hospitalizations (first and recurrent) in comparison to placebo. (4) To evaluate the efficacy of MK-1242 (vericiguat) in increasing the time to the first occurrence of the composite of all-cause mortality or HF hospitalization in comparison to placebo. (5) To evaluate the efficacy of MK-1242 (vericiguat) in increasing the time to all-cause mortality in comparison to placebo. (6) To evaluate the safety and tolerability of MK-1242 (vericiguat). ;Primary end point(s): The primary endpoint of the study is the time-to first occurrence of the composite of CV death or HF hospitalization. This endpoint integrates the cause-specific components CV death and HF hospitalization and is the most frequently used primary endpoint in recent Phase III HFrEF trials. Subjects without a HF hospitalization or CV death at the time of analysis will be censored at the time of a non-CV death or time of last information available for subjects still alive at time of analysis.;Timepoint(s) of evaluation of this end point: Effort will be made to follow-up subjects that prematurely stop study medication to collect at least information for the primary endpoint. The time point of final analysis will be based on number of CV deaths. In addition to the final analysis, an interim analysis for efficacy is | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary study endpoints are: • Components of the primary composite endpoint: - 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 ;Timepoint(s) of evaluation of this end point: Analogous to the analysis of the primary endpoint, the analysis of the secondary efficacy endpoints will be performed under the intention to treat principle. All subjects randomized will be included in the analysis. Subjects will be analyzed as randomized. In addition to the final study analyses, at the efficacy interim analysis the primary endpoint and the secondary endpoint of time to CV death will be tested. The study can only be terminated early for success if both the primary endpoint and the CV death endpoint are statistically significant based on the pre-specified interim analysis boundaries. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Venezuela, Bolivarian Republic of, Vietnam
Contacts
Public ContactPatel J. Mahesh
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed