Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
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
- 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
- Are currently hospitalized with the primary reason of HF, or had an HF event within
6 months prior to screening
- Are established on regional standard-of-care HF therapies for at least 30 days prior to screening
- Systolic blood pressure ≤ 130 mmHg and diastolic blood pressure ≤ 90 mmHg
Exclusion Criteria:
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 acute coronary syndrome, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization 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
- 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 previously received omecamtiv mecarbil
- 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