Heart Failure
Conditions
Keywords
Intravenous, IV, Left Ventricular Systolic Dysfunction, Hospitalized, Acute heart failure, Heart failure, Left ventricular ejection fraction, pharmacokinetics, Pharmacodynamics, Dyspnea, hospitalization, In-patient, Omecamtiv mecarbil, Double-blind, Randomized, Placebo-controlled
Brief summary
The primary objective of the study is to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared with placebo on dyspnea in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure. This is a multicenter, randomized, double-blind, placebo-controlled study with 3 dose cohorts enrolled sequentially in order of ascending dose strength of omecamtiv mecarbil. In each cohort, subjects are randomized 1:1 to omecamtiv mecarbil or placebo.
Detailed description
This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.
Interventions
DRUGPlacebo
48-hour infusion of placebo
48-hour infusion of omecamtiv mecarbil; dose strength will depend on cohort assignment.
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
* Male or female 18 - 85 years * Hospitalized for worsening heart failure, within 24 hours of initiating IV loop diuretic * Dyspnea due to heart failure, at rest or with minimal exertion * History of left ventricular ejection fraction (LVEF) ≤ 40% * Elevated brain natriuretic peptide (BNP) or N-terminal fragment BNP (NT-proBNP)
Exclusion criteria
* Receiving IV vasopressor (excluding low dopamine), inotropic or mechanical support * Acute coronary syndrome (ACS) * Within 30 days prior to enrollment: cardiac resynchronization therapy (CRT) or implantable cardioverter defibrillator (ICD) implantation, ACS, coronary revascularization, transient ischemic attack (TIA) or stroke, sustained ventricular arrhythmia, or major surgery * Severe valvular stenosis, hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease * Estimated glomerular filtration rate (eGFR) \< 20 mL/min/1.73m2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared with placebo on dyspnea in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure. | 48 hours |
Secondary
| Measure | Time frame |
|---|---|
| To characterize pharmacokinetics of omecamtiv mecarbil including metabolites following IV infusion and to evaluate the relationship between omecamtiv mecarbil plasma concentration and echocardiographic parameters in subjects with AHF | 48 hours |
| To assess the safety and tolerability of 3 dose levels of IV omecamtiv mecarbil compared with placebo in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure | 48 hours |
| To evaluate the effects of 48 hours treatment with IV omecamtiv mecarbil on additional measures of dyspnea, patient global assessment (PGA), change in NT-proBNP, incidence of worsening heart failure, and short term clinical outcomes | 48 hours |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, Finland, France, Germany, Greece, Hungary, Italy, Lithuania, Netherlands, Norway, Poland, Russia, Slovakia, United Kingdom, United States
Outcome results
None listed