Heart Failure, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
CK-1827452, omecamtiv mecarbil
Brief summary
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.
Detailed 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.
Interventions
Oral Tablet
DRUGPlacebo
Oral Tablet
Sponsors
Cytokinetics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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 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
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the first of event of CV death, HF event, 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of CV death and HF event |
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of HF hospitalization |
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of HF outcomes in patients with severe HF, defined as patients with NYHA class 3-4 symptoms and a HF event within the last 3 months |
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of irreversible morbidity/mortality related to HFrEF |
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of CV mortality |
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of stroke |
| 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 | Effect of omecamtiv mecarbil compared with placebo on risk of all-cause mortality |
Countries
Canada, China, France, Germany, Greece, Italy, Poland, Spain, United Kingdom, United States
Contacts
CONTACTCytokinetics MD
STUDY_DIRECTORCytokinetics MD
Cytokinetics
Outcome results
None listed