Clinical trial NCT01300013: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
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
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 614
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 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.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 48 hours
Secondary outcomes:
measure: 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
timeFrame: 48 hours
measure: 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
timeFrame: 48 hours
measure: 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
timeFrame: 48 hours
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Inglewood
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Danbury
country: United States
facility: Research Site
state: Connecticut
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Atlantis
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Novi
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Newark
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Cortlandt Manor
country: United States
facility: Research Site
state: New York
city: Roslyn
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Fairfield
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Tullahoma
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Murray
country: United States
facility: Research Site
state: Utah
city: Darlinghurst
country: Australia
facility: Research Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Research Site
state: Queensland
city: Bedford Park
country: Australia
facility: Research Site
state: South Australia
city: Prahran
country: Australia
facility: Research Site
state: Victoria
city: Richmond
country: Australia
facility: Research Site
state: Victoria
city: Aalst
country: Belgium
facility: Research Site
city: Bonheiden
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Blagoevgrad
country: Bulgaria
facility: Research Site
city: Kazanlak
country: Bulgaria
facility: Research Site
city: Pazardzhik
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sandanski
country: Bulgaria
facility: Research Site
city: Smolyan
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: QuÃ©bec
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Usti nad Labem
country: Czechia
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Turku
country: Finland
facility: Research Site
city: Caen Cedex 9
country: France
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Montpellier cedex 05
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse Cedex 09
country: France
facility: Research Site
city: Bad Nauheim
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Greifswald
country: Germany
facility: Research Site
city: Halle/Saale
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Homburg
country: Germany
facility: Research Site
city: Langen
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: WÃ¼rzburg
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Haidari
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Patra
country: Greece
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Pecs
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Cagliari
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Udine
country: Italy
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Delft
country: Netherlands
facility: Research Site
city: Deventer
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Stavanger
country: Norway
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St.-Petrsburg
country: Russian Federation
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Nitra
country: Slovakia
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Cottingham
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Teerlink JR, Felker GM, McMurray JJV, Ponikowski P, Metra M, Filippatos GS, Ezekowitz JA, Dickstein K, Cleland JGF, Kim JB, Lei L, Knusel B, Wolff AA, Malik FI, Wasserman SM; ATOMIC-AHF Investigators. Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study. J Am Coll Cardiol. 2016 Mar 29;67(12):1444-1455. doi: 10.1016/j.jacc.2016.01.031.