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Phase 3 N=6,105 Randomized Quadruple-blind Treatment

A Study of Vericiguat (MK-1242) in Participants With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-035)

Chronic Heart Failure With Reduced Ejection Fraction

Enrolled (actual)
6,105
Serious AEs
24.6%
Results posted
Dec 2025
Primary outcome: Primary: Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years — 11.3; 12.2 Pts. with event/100 patient-yrs at risk — p=0.219

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Vericiguat (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Merck Sharp & Dohme LLC
Primary completion
Nov 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years
11.3; 12.2 0.219
SECONDARY
Time to CV Death: Participants With an Event Per 100 Patient-Years
5.7; 6.8 0.020 sig
SECONDARY
Time to First Occurrence of HF Hospitalization: Participants With an Event Per 100 Patient-Years
7.2; 7.6 0.509
SECONDARY
Time to Total HF Hospitalizations (Including First and Recurrent Events): Total Events Per 100 Patient-Years
10.7; 11.8 0.094
SECONDARY
Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization: Participants With an Event Per 100 Patient-Years
12.7; 13.9 0.116
SECONDARY
Time to All-Cause Mortality: Participants With an Event Per 100 Patient-Years
7.3; 8.6 0.015 sig
SECONDARY
Percentage of Participants Who Experienced One or More Selected Nonserious Adverse Events (NSAEs)
19.7; 16.9
SECONDARY
Percentage of Participants Who Experienced One or More Serious Adverse Events (SAEs)
23.5; 24.6
SECONDARY
Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECIs)
17.6; 14.6
SECONDARY
Percentage of Participants Who Experienced One or More Potential DILI ECIs
0.3; 0.4 0.512
SECONDARY
Percentage of Participants Who Experienced One or More Symptomatic Hypotension ECIs
11.3; 9.2 0.007 sig
SECONDARY
Percentage of Participants Who Experienced One or More Anemia ECIs
7.6; 6.3 0.045 sig

Summary

The purpose of this study is to evaluate the efficacy and safety of vericiguat in participants with chronic heart failure with reduced ejection fraction (HFrEF), specifically those with symptomatic chronic HFrEF who have not had a recent hospitalization for heart failure or need for outpatient intravenous (IV) diuretics. The primary hypothesis is that vericiguat is superior to placebo in reducing the risk of cardiovascular death or heart failure hospitalization.

Eligibility Criteria

Inclusion Criteria

  • History of chronic HF [New York Heart Association (NYHA) Class II to IV] on guideline-directed medical therapy for heart failure (GDMT) with no HF hospitalization within 6 months or outpatient IV diuretic use within 3 months before randomization.
  • Left ventricular ejection fraction (LVEF) of ≤40%, assessed within 12 months before randomization by any imaging method.
  • Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during the study intervention period and for at least 1 month after the last dose of study intervention.

Exclusion Criteria

  • Has SBP <100 mm Hg or symptomatic hypotension.
  • Awaiting heart transplantation, is receiving continuous IV infusion of an inotrope, or has or anticipates receiving an implanted ventricular assist device.
  • Amyloidosis or sarcoidosis.
  • Primary valvular heart disease requiring surgical procedure or intervention or has undergone a valvular surgical procedure or intervention within 3 months before randomization.
  • Hypertrophic cardiomyopathy.
  • Acute myocarditis or Takotsubo cardiomyopathy.
  • History of heart transplant.
  • Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
  • Acute coronary syndrome, or undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3 months before randomization.
  • History of symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3 months before randomization.
  • Malignancy or other noncardiac condition limiting life expectancy to <3 years.
  • Requires continuous home oxygen for severe pulmonary disease.
  • Interstitial lung disease.
  • Discontinuation or dose modification of GDMT or vericiguat within 4 weeks before randomization.
  • Recent history (within the last year) of drug or alcohol abuse or dependence.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05093933). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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