A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial to Assess Efficacy and Safety of Omecamtiv Mecarbil in Patients With Symptomatic Heart Failure With Severely Reduced Ejection Fraction (COMET-HF)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,800
- 试验地点
- 350
- 主要终点
- Time to the first of event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke
研究概览
简要总结
The purpose of this study is to find out if the investigational drug called omecamtiv mecarbil can reduce the risk of the effects of heart failure, like hospitalization, transplantation, or death in patients with heart failure and severely reduced ejection fraction.
详细描述
This study is designed to evaluate the efficacy and safety of omecamtiv mecarbil in reducing the risk of the primary composite endpoint of cardiovascular (CV) death, first heart failure (HF) event, left ventricular assist device (LVAD) implantation, cardiac transplantation, and stroke in patients with symptomatic heart failure with severely reduced ejection fraction (HFrEF).
Eligible patients will be randomized 1:1 to investigational product (IP) - omecamtiv mecarbil or placebo. The study is event-driven and will conclude when at least 850 participants experience a HF event or CV death, whichever comes first. An interim analysis for futility and efficacy based on the primary composite endpoint is planned when approximately 570 (67%) of the planned 850 first HF events or CV deaths are observed.
Estimated duration of participation: Up to 3 years.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients who meet all the following criteria at screening may be included in the study:
- •Are between ≥ 18 years and ≤ 85 years at the signing of informed consent
- •Have a history of chronic HFrEF, defined as requiring treatment for HF for a minimum of 3 months prior to screening
- •Are receiving oral loop diuretics on a regular schedule
- •Patients without AFF on screening ECG:
- •LVEF < 30% within 6 months of screening
- •Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 1000 pg/mL (BNP ≥ 300 pg/mL)
- •Patients with AFF on screening ECG:
- •LVEF < 25% within 6 months of screening
- •Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 3000 pg/mL (BNP ≥ 900 pg/mL)
- •Not currently taking digoxin
- •Meet one of the following criteria for a recent HF event:
- •Are currently hospitalized with the primary reason of HF
- •Had an HF event (as defined in the primary endpoint) within 12 months prior to screening. For the purposes of a qualifying HF event, subcutaneous furosemide will be treated as equivalent to intravenous furosemide Or
- •Had outpatient escalation of oral diuretics due to worsening signs and symptoms of heart failure plus one of two additional criteria sustained for at least 1 week: (1) at least 50% or 1.5-fold increase in daily loop-diuretic-equivalent dose; (2) the addition of a new diuretic class to a loop diuretic.
- •Are established on regional standard-of-care HF therapies for at least 30 days prior to screening
- •Systolic blood pressure ≤ 140 mmHg
排除标准
- •Any of the following criteria will exclude potential patients from the study:
- •Have AFF on the screening ECG and are currently taking digoxin
- •Have had any event or procedure that may have resulted in a change in ejection fraction, including, but not limited to, acute coronary syndrome and/or any coronary revascularization, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization, or cardiac contractility modulation therapy within 3 months of screening
- •Are admitted to a long-term care facility or hospice
- •Have a projected survival of < 12 months due to non-cardiovascular causes based on clinical judgment
- •Are receiving intravenous inotropes or intravenous vasopressors ≤ 3 days prior to screening
- •Are receiving mechanical hemodynamic support or mechanical ventilation ≤ 7 days prior to screening
- •Are receiving intravenous diuretics, intravenous vasodilators, or supplemental oxygen therapy ≤ 12 hours prior to screening (except for nocturnal supplemental oxygen for sleep apnea or heart failure)
- •Have an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 or receiving dialysis at screening
- •Have previously had a solid organ transplant
- •Are receiving treatment in another investigational device or drug study or are within 30 days of ending such investigational treatment at screening
- •Have received omecamtiv mecarbil in a previous clinical trial
- •Are pregnant or planning pregnancy during the study period, or planning to breastfeed during treatment with IP or within 5 days after the end of treatment with IP
- •Have primary infiltrative cardiomyopathy (e.g. cardiac amyloidosis) or severe stenotic valvular disease
研究组 & 干预措施
Placebo
Participants randomized to placebo will receive placebo twice daily until at least 850 participants experience a HF event or CV death, whichever comes first.
干预措施: Placebo (Drug)
Omecamtiv Mecarbil
Participants randomized to omecamtiv mecarbil will be dosed based on their omecamtiv mecarbil plasma concentration at 25, 37.5 or 50 mg twice daily until at least 850 participants experience a HF event or CV death, whichever comes first.
干预措施: Omecamtiv Mecarbil (OM) (Drug)
结局指标
主要结局
Time to the first of event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke
时间窗: From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years
Efficacy of omecamtiv mecarbil compared with placebo on the risk of HF outcomes in patients with symptomatic HFrEF and severely reduced ejection fraction in the setting of guideline-directed medical therapy per local standard of care.
次要结局
- Time to the first event of CV death or HF event(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)
- Time to the first HF hospitalization(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)
- Time to the first event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke in a subgroup of patients with severe HF(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)
- Time to the first event of CV death, LVAD implantation/cardiac transplantation, or stroke(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)
- Time to CV death(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)
- Time to first event of stroke(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)
- Time to all-cause death(From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years)