Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure (ATOMIC-AHF)

Phase 2

Completed

• Conditions: Heart Failure
• Interventions: Drug: Placebo; Drug: Omecamtiv mecarbil

• Registration Number: NCT01300013
• Lead Sponsor: Cytokinetics

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.

Study Timeline

• Study First Submitted: 2011-02-17
• Study First Submitted QC: 2011-02-17
• Study First Posted: 2011-02-21
• Study Start: 2011-04
• Primary Completion: 2013-04
• Study Completion: 2013-09
• Disposition First Submitted: 2014-01-15
• Disposition First Submitted QC: 2014-01-15
• Disposition First Posted: 2014-02-12
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-25
• Last Update Posted: 2021-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 614

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Omecamtiv mecarbil	Omecamtiv mecarbil	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Research Site; 🇬🇧 Harrow, United Kingdom