A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001)
Condition: Heart Failure; Chronic Heart Failure With Reduced Ejection Fraction
MeSH terms: Heart Failure
Intervention: Vericiguat; Placebo for vericiguat
Intervention description: 2.5, 5.0, or 10.0 mg orally once daily; 2.5, 5.0, or 10.0 mg orally once daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 5050.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, placebo-controlled, parallel-group, multi-center, double-blind, event
      driven study of vericiguat (MK-1242) in participants with heart failure with reduced ejection
      fraction (HFrEF). The primary hypothesis is vericiguat (MK-1242) is superior to placebo in
      increasing the time to first occurrence of the composite of cardiovascular (CV) death or
      heart failure (HF) hospitalization in participants with HFrEF.
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of chronic HF (New York Heart Association [NYHA] Class II-IV) on standard
             therapy before qualifying HF decompensation

          -  Previous HF hospitalization within 6 months prior to randomization or intravenous (IV)
             diuretic treatment for HF (without hospitalization) within 3 months.

          -  Brain natriuretic peptide (BNP) levels: sinus rhythm-≥ 300 pg/mL; atrial
             fibrillation-≥ 500 pg/mL and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP)
             levels: sinus rhythm- ≥ 1000 pg/mL; atrial fibrillation - ≥ 1600 pg/mL within 30 days
             prior to randomization

          -  Left ventricular ejection fraction (LVEF) of <45% assessed within 12 months prior to
             randomization by any method

          -  If female, is not of reproductive potential or agrees to avoid becoming pregnant while
             receiving study drug and for 14 days after the last dose of study drug by complying
             with one of the following: practice abstinence from heterosexual activity or use (or
             have her partner use) acceptable contraception during heterosexual activity.

        Exclusion Criteria:

          -  Clinically unstable at the time of randomization as defined by either the
             administration of any IV treatment within 24 hours prior to randomization, and/or
             systolic blood pressure (SBP) <100 mmHg or symptomatic hypotension

          -  Current or anticipated use of long-acting nitrates or nitric oxide (NO) donors
             including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol
             tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine

          -  Current or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors such as
             vardenafil, tadalafil, and sildenafil

          -  Current use or anticipated use of a soluble guanylate cyclase (sGC) stimulator such as
             riociguat

          -  Known allergy or sensitivity to any sGC stimulator

          -  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

          -  Primary valvular heart disease requiring surgery or intervention, or is within 3
             months after valvular surgery or intervention

          -  Hypertrophic obstructive cardiomyopathy

          -  Acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy

          -  Post-heart transplant cardiomyopathy

          -  Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia

          -  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, or indication for coronary revascularization at
             time of randomization

          -  Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days

          -  Complex congenital heart disease

          -  Active endocarditis or constrictive pericarditis

          -  Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 or chronic dialysis

          -  Severe hepatic insufficiency such as with hepatic encephalopathy

          -  Malignancy or other non-cardiac condition limiting life expectancy to <3 years

          -  Require continuous home oxygen for severe pulmonary disease

          -  Current alcohol and/or drug abuse

          -  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

          -  Mental or legal incapacitation and is unable to provide informed consent

          -  Immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is
             involved with this study

          -  Interstitial Lung Disease

          -  Is pregnant or breastfeeding or plans to become pregnant or to breastfeed during the
             course of the study