Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction
Purpose
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.
Conditions
- Heart Failure
- Heart Failure With Reduced Ejection Fraction
Eligibility
- Eligible Ages
- Between 18 Years and 85 Years
- Eligible Sex
- All
- Accepts 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Placebo Comparator 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. |
|
Recruiting Locations
Alexander City, Alabama 35010
Birmingham, Alabama 35233
Beverly Hills, California 90211
La Jolla, California 92037
Loma Linda, California 92350
Los Angeles, California 90033
Los Angeles, California 90095
Orange, California 92868
Sacramento, California 95816
Sacramento, California 95817
San Diego, California 92123
San Francisco, California 94109
Santa Clara, California 95051
Stanford, California 94303
Torrance, California 90502
Aurora, Colorado 80045
Bridgeport, Connecticut 06606
Hartford, Connecticut 06102
New Haven, Connecticut 06519
Clearwater, Florida 33756
Fort Lauderdale, Florida 33308
Hollywood, Florida 33351
Jacksonville, Florida 32209
Miami Beach, Florida 33140
Ocala, Florida 34471
Orlando, Florida 32803
Tampa, Florida 33606
Atlanta, Georgia 30303
Atlanta, Georgia 30309
Atlanta, Georgia 30322
Fayetteville, Georgia 30214
Honolulu, Hawaii 96813
Naperville, Illinois 60540
Munster, Indiana 46321
Newburgh, Indiana 47630
Richmond, Indiana 47374
Kansas City, Kansas 66160
Overland Park, Kansas 66211
New Orleans, Louisiana 70112
Bangor, Maine 04401
Baltimore, Maryland 21201
Boston, Massachusetts 02111
Detroit, Michigan 48202
Independence, Missouri 64057
Kansas City, Missouri 64111
St Louis, Missouri 63110
Omaha, Nebraska 68198
Bridgewater, New Jersey 08807
Eatontown, New Jersey 07724
Albany, New York 12205
Manhasset, New York 11030
New York, New York 10029
New York, New York 10032
The Bronx, New York 10467
Cary, North Carolina 27518
Chapel Hill, North Carolina 27599-7064
Durham, North Carolina 27710
Greensboro, North Carolina 27401
Winston-Salem, North Carolina 27157
Cincinnati, Ohio 45219
Cleveland, Ohio 44106
Cleveland, Ohio 44195
Sandusky, Ohio 44870
Tulsa, Oklahoma 74127
Portland, Oregon 97239
Camp Hill, Pennsylvania 17011
Hershey, Pennsylvania 17033
Philadelphia, Pennsylvania 19104
Charleston, South Carolina 29425
Rapid City, South Dakota 57701
Germantown, Tennessee 38138
Knoxville, Tennessee 37934
Nashville, Tennessee 37232
Tullahoma, Tennessee 37388
Dallas, Texas 75246
Dallas, Texas 75390
El Paso, Texas 79902
Galveston, Texas 77555
Houston, Texas 77030
Plano, Texas 75093
Murray, Utah 84107
Salt Lake City, Utah 84132
Norfolk, Virginia 23507
Spokane, Washington 99204
Milwaukee, Wisconsin 53226
More Details
- Status
- Recruiting
- Sponsor
- Cytokinetics
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.