COMET-HF

Currently Recruiting: Participants and Sites

Study Drug/Intervention: Omecamtiv Mecarbil

Anticipated Sample Size: 1,800 patients

Study Timeline: This study is expected to conclude in April 2028.

ClinicalTrials.gov ID:  NCT06736574

What is COMET-HF?

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 (HFrEF).

Study Objective

The primary objective is to evaluate the efficacy of omecamtiv mecarbil compared with placebo on risk of heart failure outcomes in patients with symptomatic HFrEF and severely reduced ejection fraction in the setting of guideline-directed medical therapy per local standard of care.

Inclusion Criteria

Patients must meet all of the following criteria:

1. Are between ≥ 18 years and ≤ 85 years at the signing of informed consent
2. Have a history of chronic HFrEF, defined as requiring treatment for HF for a minimum of 3 months prior to screening
3. Are receiving oral loop diuretics
4. Have an LVEF < 30% measured within the previous 6 months
   1. Patients with AFF must have an LVEF < 25%.*,**
5. Are currently hospitalized with the primary reason of HF or had an HF event within 6 months prior to screening.
6. Are established on standard-of-care HF therapies (e.g., beta blockers, renin-angiotensin-aldosterone system inhibitors, sodium-glucose co-transporter 2 inhibitors) consistent with physician discretion and regional clinical practice guidelines for at least 30 days prior to screening.
   1. Patients enrolled either during HF hospitalization or soon after HF hospitalization discharge can be reinitiating or titrating oral, standard-of-care, chronic HF therapies at the same time of randomization to achieve optimized therapy on-study.
7. Systolic blood pressure ≤ 130 mmHg and diastolic blood pressure ≤ 90 mmHg.
8. Have elevated natriuretic peptide (BNP or NT-proBNP) levels at screening:
   1. Patients without AFF on the screening electrocardiogram (ECG): BNP ≥ 300 pg/mL or NT-proBNP ≥ 1,000 pg/mL
   2. Patients with AFF on the screening ECG: BNP ≥ 900 pg/mL or NT-proBNP ≥ 3,000 pg/mL
9. Are able to comprehend and willing to sign an ICF and willing to comply with all study procedures and restrictions for the duration specified in the Schedule of Activities (Section 1.3).
10. A female patient is eligible to participate if she is not pregnant, breastfeeding, or planning to donate eggs, and at least one of the following conditions applies:
    1. Is not a woman of childbearing potential (WOCBP); OR
    2. Is a WOCBP using a highly effective or acceptable method of contraception (Appendix 3 (Section 10.3) and her male partner agrees to use a condom, during the trial and for at least 4 weeks after the last dose of IP. A WOCBP must have a negative pregnancy test (urine or serum).

*Note: AFF on screening ECG is capped at 15% of study patients.
**Note: LVEF must be confirmed by an EF measurement (e.g, local or core echocardiography, cardiac magnetic resonance imaging, or other) performed within 6 months prior to screening, and at least 3 months after acute coronary syndrome, cardiac surgery, valve procedures, any coronary revascularization, and/or cardiac resynchronization therapy. In the absence of an echocardiogram prior to screening, one will be required at screening.

Exclusion Criteria

Patients will be excluded from the study if any of the following criteria apply:

11. Have AFF on the screening ECG and are currently taking digoxin
12. Have had acute coronary syndrome, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization therapy within 3 months of screening
    1. Acute coronary syndrome includes ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, and unstable angina requiring hospitalization.
13. Are admitted to a long-term care facility or hospice
14. Have a projected survival of < 12 months due to non-cardiovascular causes (e.g., malignancy) based on clinical judgment
15. Are receiving intravenous inotropes (e.g., dobutamine, milrinone, levosimendan) or intravenous vasopressors (e.g., epinephrine, norepinephrine, dopamine, or vasopressin) ≤ 3 days prior to screening
16. Are receiving mechanical hemodynamic support (e.g., intra-aortic balloon pump counterpulsation), or mechanical ventilation (including non-invasive mechanical ventilation, i.e., bilevel positive airway pressure or continuous positive airway pressure devices) ≤ 7 days prior to screening
17. Are receiving intravenous diuretics, intravenous vasodilators, or supplemental oxygen therapy ≤ 12 hours prior to screening
18. Have an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 or receiving dialysis at screening
19. Have previously had a solid organ transplant
20. Are receiving treatment in another investigational device or drug study or are within 30 days (or 5 half-lives for drugs, whichever is longer) of ending such investigational treatment at screening. Other investigational procedures while participating in this study are not permitted.
21. Have previously received omecamtiv mecarbil
22. Are not able to swallow the IP tablet (e.g., swallowing disorders, feeding tubes)
23. Have a history or evidence of any other clinically significant disorder, condition, or disease (except those outlined previously) that, in the opinion of the investigator, if consulted, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion
24. Are pregnant or planning pregnancy during the study period, or planning to breastfeed during treatment with IP (omecamtiv mecarbil or placebo) or within 5 days after the end of treatment with IP

The study population will include adults with symptomatic heart failure with severely reduced ejection fraction (HFrEF) and will be recruited globally from different sites.

Study Sites

Active US Sites include: 

• Advanced Cardiovascular LLC- Alexander City, Alabama
• Cardiovascular Research of Northwest Indiana- Muster, Indiana 
• K&R Research- Marion, Ohio
• Ocala Cardiovascular Center- Ocala, Florida
• Capital Area Research, LLC- Camp Hill, Pennsylvania

Duration of Study Participation

Up to 3 years

Study Follow-Up

A follow-up visit will occur 4 weeks after the last investigational product dose.

Cytokinetics

• PI: G. Michael Felker, MD, MHS
• PL: Kelly Mundy