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)

This study has been completed.
Sponsor:
Collaborator:
Cytokinetics
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01300013
First received: February 17, 2011
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Drug: Placebo
Drug: Omecamtiv mecarbil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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. [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Enrollment: 614
Study Start Date: April 2011
Study Completion Date: September 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omecamtiv mecarbil Drug: Omecamtiv mecarbil
48-hour infusion of omecamtiv mecarbil; dose strength will depend on cohort assignment.
Other Names:
  • CK-1827452
  • AMG 423
Placebo Comparator: Placebo Drug: Placebo
48-hour infusion of placebo

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01300013

  Show 150 Study Locations
Sponsors and Collaborators
Amgen
Cytokinetics
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01300013     History of Changes
Other Study ID Numbers: 20100754
Study First Received: February 17, 2011
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Amgen:
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

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases
Ventricular Dysfunction

ClinicalTrials.gov processed this record on September 16, 2014