Clinical trial NCT06736574: Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Heart Failure
Heart Failure With Reduced Ejection Fraction
Keywords: CK-1827452
omecamtiv mecarbil
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2024-12-16
Enrollment: 1800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to the first of event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke
timeFrame: 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
Secondary outcomes:
measure: Time to the first event of CV death or HF event
timeFrame: 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
measure: Time to the first HF hospitalization
timeFrame: 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
measure: Time to the first event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke in a subgroup of patients with severe HF
timeFrame: 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
measure: Time to the first event of CV death, LVAD implantation/cardiac transplantation, or stroke
timeFrame: 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
measure: Time to CV death
timeFrame: 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
measure: Time to first event of stroke
timeFrame: 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
measure: Time to all-cause death
timeFrame: 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
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Advanced Cardiovascular, LLC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Pima Heart and Vascular Clinical Research
state: Arizona
city: Beverly Hills
country: United States
facility: National Heart Institute
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center of USC (outpatient clinic)
state: California
city: San Diego
country: United States
facility: San Diego Cardiac Center
state: California
city: Bridgeport
country: United States
facility: Cardiology Associates of Fairfield County, P.C
state: Connecticut
city: Clearwater
country: United States
facility: CHF Heart Clinical (Subject Visits & IP Shipments)
state: Florida
city: Hollywood
country: United States
facility: South Florida Research Solutions, LLC
state: Florida
city: Miami Beach
country: United States
facility: Broward Research Center
state: Florida
city: Ocala
country: United States
facility: Ocala Cardiovascular Research
state: Florida
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute
state: Illinois
city: Munster
country: United States
facility: Cardiovascular Research of Northwest Indiana, LLC.
state: Indiana
city: Richmond
country: United States
facility: Reid Physician Associates
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Bangor
country: United States
facility: Eastern Main Medical Center dba Northern Light Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Independence
country: United States
facility: Midwest Heart and Vascular Specialists, LLC
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: St. Louis
country: United States
facility: Washington University Center for Advanced Medicine
state: Missouri
city: St. Louis
country: United States
facility: St. Louis Heart and Vascular
state: Missouri
city: Bridgewater
country: United States
facility: Advanced Heart Care, LLC
state: New Jersey
city: Eatontown
country: United States
facility: Monmouth Cardiology Associates, LLC
state: New Jersey
city: Albany
country: United States
facility: Capital Cardiology Associates
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center (Moses Campus)
state: New York
city: Greensboro
country: United States
facility: Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health
state: North Carolina
city: Marion
country: United States
facility: K&R Research LLC
state: Ohio
city: Camp Hill
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Rapid City
country: United States
facility: Monument Health Clinical Research, a department of Monument Health Rapid City Hospital, Inc.
state: South Dakota
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: El Paso
country: United States
facility: Medresearch Inc
state: Texas
Study officials:
affiliation: Cytokinetics
name: Cytokinetics MD
role: STUDY_DIRECTOR
References: