A Pivotal Phase 3 Randomized, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of the sGC Stimulator Vericiguat/MK-1242 in Adults With Chronic Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 6,106
- 试验地点
- 519
- 主要终点
- Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Vericiguat
Participants receive a starting dose of 2.5 mg of vericiguat taken orally once daily. The vericiguat dose will be titrated to 5 mg and to 10 mg.
干预措施: Vericiguat (Drug)
Placebo
Participants receive a starting matching placebo to vericiguat dose of 2.5 mg taken orally once daily. The matching placebo dose will be sham titrated to 5 mg and to 10 mg.
干预措施: Placebo (Drug)
结局指标
主要结局
Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years
时间窗: Up to approximately 36 months (from randomization to the primary completion data cutoff)
The time to first occurrence of the composite endpoint of CV death or HF hospitalization was defined as the time from randomization to the first event of CV death or HF hospitalization. Randomized participants without a HF hospitalization or CV death event at the time of analysis were censored at the last available information, when the protocol pre-specified number of total CV death events was achieved (primary completion analysis data cutoff), or the date of their non-CV death, whichever occurred first. Events were confirmed by a clinical events committee (CEC). Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with a CV death or HF hospitalization event per 100 patient-years at risk is presented.
次要结局
- Time to CV Death: Participants With an Event Per 100 Patient-Years(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Time to First Occurrence of HF Hospitalization: Participants With an Event Per 100 Patient-Years(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Time to Total HF Hospitalizations (Including First and Recurrent Events): Total Events Per 100 Patient-Years(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization: Participants With an Event Per 100 Patient-Years(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Time to All-Cause Mortality: Participants With an Event Per 100 Patient-Years(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Percentage of Participants Who Experienced One or More Selected Nonserious Adverse Events (NSAEs)(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Percentage of Participants Who Experienced One or More Serious Adverse Events (SAEs)(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECIs)(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Percentage of Participants Who Experienced One or More Potential DILI ECIs(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Percentage of Participants Who Experienced One or More Symptomatic Hypotension ECIs(Up to approximately 36 months (from randomization to the primary completion data cutoff))
- Percentage of Participants Who Experienced One or More Anemia ECIs(Up to approximately 36 months (from randomization to the primary completion data cutoff))