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NCT06736574PHASE3Recruiting

Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction

Cytokinetics

Start Date

12/19/2024

Completion Date

12/1/2027

Summary

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.

Detailed Description

This study is designed to evaluate the efficacy and safety of omecamtiv mecarbil in reducing the risk of the primary composite endpoint of cardiovascular (CV) death, first heart failure (HF) event, left ventricular assist device (LVAD) implantation, cardiac transplantation, and stroke in patients with symptomatic heart failure with severely reduced ejection fraction (HFrEF). Eligible patients will be randomized 1:1 to investigational product (IP) - omecamtiv mecarbil or placebo. The study is event-driven and will conclude when at least 850 participants experience a HF event or CV death, whichever comes first. An interim analysis for futility and efficacy based on the primary composite endpoint is planned when approximately 570 (67%) of the planned 850 first HF events or CV deaths are observed. Estimated duration of participation: Up to 3 years.

Eligibility Criteria

Age Range: 18 years to 85 years

Inclusion Criteria: Adult patients who meet all the following criteria at screening may be included in the study: * Are between ≥ 18 years and ≤ 85 years at the signing of informed consent * Have a history of chronic HFrEF, defined as requiring treatment for HF for a minimum of 3 months prior to screening * Are receiving oral loop diuretics on a regular schedule * Patients without AFF on screening ECG: * LVEF \< 30% within 6 months of screening * Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 1000 pg/mL (BNP ≥ 300 pg/mL) * Patients with AFF on screening ECG: * LVEF \< 25% within 6 months of screening * Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 3000 pg/mL (BNP ≥ 900 pg/mL) * Not currently taking digoxin * Meet one of the following criteria for a recent HF event: * Are currently hospitalized with the primary reason of HF * Had an HF event (as defined in the primary endpoint) within 12 months prior to screening. For the purposes of a qualifying HF event, subcutaneous furosemide will be treated as equivalent to intravenous furosemide Or * Had outpatient escalation of oral diuretics due to worsening signs and symptoms of heart failure plus one of two additional criteria sustained for at least 1 week: (1) at least 50% or 1.5-fold increase in daily loop-diuretic-equivalent dose; (2) the addition of a new diuretic class to a loop diuretic. * Are established on regional standard-of-care HF therapies for at least 30 days prior to screening * Systolic blood pressure ≤ 140 mmHg Exclusion Criteria: Any of the following criteria will exclude potential patients from the study: * Have AFF on the screening ECG and are currently taking digoxin * Have had any event or procedure that may have resulted in a change in ejection fraction, including, but not limited to, acute coronary syndrome and/or any coronary revascularization, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization, or cardiac contractility modulation therapy within 3 months of screening * Are admitted to a long-term care facility or hospice * Have a projected survival of \< 12 months due to non-cardiovascular causes based on clinical judgment * Are receiving intravenous inotropes or intravenous vasopressors ≤ 3 days prior to screening * Are receiving mechanical hemodynamic support or mechanical ventilation ≤ 7 days prior to screening * Are receiving intravenous diuretics, intravenous vasodilators, or supplemental oxygen therapy ≤ 12 hours prior to screening (except for nocturnal supplemental oxygen for sleep apnea or heart failure) * Have an estimated glomerular filtration rate (eGFR) \< 20 mL/min/1.73m2 or receiving dialysis at screening * Have previously had a solid organ transplant * Are receiving treatment in another investigational device or drug study or are within 30 days of ending such investigational treatment at screening * Have received omecamtiv mecarbil in a previous clinical trial * Are pregnant or planning pregnancy during the study period, or planning to breastfeed during treatment with IP or within 5 days after the end of treatment with IP * Have primary infiltrative cardiomyopathy (e.g. cardiac amyloidosis) or severe stenotic valvular disease

Interventions

DRUG

Omecamtiv Mecarbil (OM)

DRUG

Placebo

Interested in This Trial?

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Conditions

Heart FailureHeart Failure With Reduced Ejection Fraction

Locations

Advanced Cardiovascular, LLC

Alexander City, Alabama 35010

United States

University of Alabama at Birmingham

Birmingham, Alabama 35233

United States

Pima Heart and Vascular Clinical Research

Tucson, Arizona 85741

United States

National Heart Institute

Beverly Hills, California 90211

United States

UC San Diego Health - Sulpizio Cardiovascular Center

La Jolla, California 92037

United States

Nutrition Research Center (SPH)

Loma Linda, California 92350

United States

Keck Medical Center of USC (outpatient clinic)

Los Angeles, California 90033

United States

UCLA Medical Center Cardiovascular Clinic

Los Angeles, California 90095

United States

University of California, Irvine Medical Center

Orange, California 92868

United States

Sutter Institute for Medical Research (SIMR)

Sacramento, California 95816

United States

UC Davis Health

Sacramento, California 95817

United States

San Diego Cardiac Center

San Diego, California 92123

United States

California Pacific Medical Center Van Ness Campus

San Francisco, California 94109

United States

Kaiser Permanente Santa Clara

Santa Clara, California 95051

United States

Stanford University Hospital / Stanford Health Care

Stanford, California 94303

United States

Lundquist Institute for Biomedical Innovation at Harbor - UCLA Medical Center

Torrance, California 90502

United States

Rocky Mountain Regional VA Medical Center

Aurora, Colorado 80045

United States

Cardiology Associates of Fairfield County, P.C

Bridgeport, Connecticut 06606

United States

Hartford Hospital

Hartford, Connecticut 06102

United States

Yale New Haven Health Heart & Vascular Center Outpatient Services

New Haven, Connecticut 06519

United States

CHF Heart Clinical (Subject Visits & IP Shipments)

Clearwater, Florida 33756

United States

Holy Cross Medical Group - Cardiology Associates

Fort Lauderdale, Florida 33308

United States

South Florida Research Solutions, LLC

Hollywood, Florida 33351

United States

UF Health Jacksonville

Jacksonville, Florida 32209

United States

Broward Research Center

Miami Beach, Florida 33140

United States

Ocala Cardiovascular Research

Ocala, Florida 34471

United States

AdventHealth

Orlando, Florida 32803

United States

USF Health South Tampa Center for Advanced Healthcare

Tampa, Florida 33606

United States

Grady Health System

Atlanta, Georgia 30303

United States

Piedmont Atlanta Hospital

Atlanta, Georgia 30309

United States

Emory Clinic

Atlanta, Georgia 30322

United States

Piedmont Fayette Hospital

Fayetteville, Georgia 30214

United States

The Queen's Medical Center - Punchbowl

Honolulu, Hawaii 96813

United States

Midwest Cardiovascular Institute

Naperville, Illinois 60540

United States

Cardiovascular Research of Northwest Indiana, LLC.

Munster, Indiana 46321

United States

Deaconess Heart Group

Newburgh, Indiana 47630

United States

Reid Physician Associates

Richmond, Indiana 47374

United States

The University of Kansas Medical Center

Kansas City, Kansas 66160

United States

AHMG Cardiology and Surgery

Overland Park, Kansas 66211

United States

University Medical Center New Orleans

New Orleans, Louisiana 70112

United States

Eastern Main Medical Center dba Northern Light Eastern Maine Medical Center

Bangor, Maine 04401

United States

University of Maryland Medical Center

Baltimore, Maryland 21201

United States

Tufts Medical Center

Boston, Massachusetts 02111

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

Midwest Heart and Vascular Specialists, LLC

Independence, Missouri 64057

United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri 64111

United States

Washington University Center for Advanced Medicine

St Louis, Missouri 63110

United States

St. Louis Heart and Vascular

St Louis, Missouri 63136

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Advanced Heart Care, LLC

Bridgewater, New Jersey 08807

United States

Monmouth Cardiology Associates, LLC

Eatontown, New Jersey 07724

United States

Capital Cardiology Associates

Albany, New York 12205

United States

Northwell Health North Shore University Hospital

Manhasset, New York 11030

United States

Mount Sinai Hospital

New York, New York 10029

United States

Columbia University Medical Center / New York - Presbyterian

New York, New York 10032

United States

Montefiore Medical Center (Moses Campus)

The Bronx, New York 10467

United States

WakeMed Heart & Vascular - Cary Cardiology

Cary, North Carolina 27518

United States

Clinical and Translational Research Center - University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599-7064

United States

Duke University Hospital

Durham, North Carolina 27710

United States

Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health

Greensboro, North Carolina 27401

United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina 27157

United States

The Lindner Research Center at the Christ Hospital

Cincinnati, Ohio 45219

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

K&R Research LLC

Marion, Ohio 43302

United States

University of Hospitals North Ohio Heart

Sandusky, Ohio 44870

United States

Oklahoma State University Center for Health Sciences

Tulsa, Oklahoma 74127

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Capital Area Research, LLC

Camp Hill, Pennsylvania 17011

United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania 17033

United States

Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)

Philadelphia, Pennsylvania 19104

United States

Medical University of South Carolina - Gazes Research Institute

Charleston, South Carolina 29425

United States

Monument Health Clinical Research, a department of Monument Health Rapid City Hospital, Inc.

Rapid City, South Dakota 57701

United States

Stern Cardiovascular Foundation, Inc.

Germantown, Tennessee 38138

United States

Tennova Healthcare-Turkey Creek Medical Center

Knoxville, Tennessee 37934

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

Tennessee Center for Clinical Trials

Tullahoma, Tennessee 37388

United States

Baylor University Medical Center

Dallas, Texas 75246

United States

The University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

Medresearch Inc

El Paso, Texas 79902

United States

University of Texas Medical Branch - UTMB

Galveston, Texas 77555

United States

CHI St. Luke's Health Baylor College of Medicine Medical Center

Houston, Texas 77030

United States

Baylor Scott & White Medical Center- The Hearth Hospital

Plano, Texas 75093

United States

Intermountain Medical Center

Murray, Utah 84107

United States

University of Utah Health

Salt Lake City, Utah 84132

United States

Sentara Norfolk General Hospital

Norfolk, Virginia 23507

United States

Providence Advanced Heart Disease and Transplant

Spokane, Washington 99204

United States

Medical College of Wisconsin / Froedtert Hospital

Milwaukee, Wisconsin 53226

United States

Mazankowski Alberta Heart Institute / University of Alberta Hospital

Edmonton, Alberta T6G2B7

Canada

Kelowna General Hospital

Kelowna, British Columbia V1Y1T2

Canada

SMH - Cardiology Clinical Trials Inc.

Surrey, British Columbia V3V0C6

Canada

St. Paul's Hospital

Vancouver, British Columbia V6Z1Y6

Canada

Victoria Heart Institute Foundation

Victoria, British Columbia V8R1B2

Canada

St. Boniface Hospital

Winnipeg, Manitoba R2H2A6

Canada

Kingston Health Sciences Centre

Kingston, Ontario K7L 2V7

Canada

London Health Sciences Centre

London, Ontario N6A5A5

Canada

Oakville Trafalgar Memorial Hospital - Halton Healthcare

Oakville, Ontario L6M0L8

Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario M4N1J7

Canada

St. Michael's Hospital

Toronto, Ontario M5B1W8

Canada

UHN-Toronto General Hospital

Toronto, Ontario M5G2C4

Canada

Montreal Heart Institute

Montreal, Quebec H1T1C8

Canada

Diex Recherche Sherbrooke

Sherbrooke, Quebec J1L0H8

Canada

CISSSL - Hopital Pierre-Le Gardeur

Terrebonne, Quebec J6V 2H2

Canada

Peking University Third Hospital

Beijing, Beijing Municipality 100032

China

Lanzhou University Second

Lanzhou, Gansu 730030

China

The Affiliated Panyu Central Hospital of Guangzhou Medical University

Guangzhou, Guangdong 511400

China

The University of Hong Kong-Shenzhen Hospital

Shenzhen, Guangdong 518053

China

The First Affiliated Hospital of Henan University of science and Technology

Luoyang, Henan 471031

China

People's Hospital of Hunan Province

Changsha, Hunan 410011

China

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu 225001

China

Heze Municipal Hospital

Heze, Shandong 274002

China

Yuncheng Central Hospital

Yuncheng, Shanxi 44000

China

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality 300020

China

Teda International Cardiovascular Hospital

Tianjin, Tianjin Municipality 300457

China

The First Affiliated Hospital of University of South China

Hengyang, 421001

China

Centre Hospitalier Universitaire de Toulouse

Toulouse, Haute-Garonne 31059

France

Polyclinique Vauban

Valenciennes, Hauts-de-France 59300

France

CHU de Rennes - Hôpital Pontchaillou

Rennes, Ille-et-Vilaine 35033

France

Centre Hospitalier Universitaire Grenoble Alpes - Site Nord Michallon

La Tronche, Isère 38700

France

CHU de Montpellier- Hôpital Arnaud de Villeneuve

Montpellier, Occitanie 34295

France

L'Hôpital Privé Du Confluent

Nantes, Pays de la Loire Region 44277

France

Hospices Civils de Lyon - Hôpital Louis Pradel

Bron, Rhône 69677

France

Centre Hospitalier Intercommunal Toulon - La Seyne sur Mer (C.H.I.T.S)

Toulon, Var 83100

France

Hôpital Lariboisière - APHP

Paris, Île-de-France Region 75010

France

Hôpital Européen Georges Pompidou

Paris, Île-de-France Region 75015

France

APHP - Hôpital Bichât

Paris, Île-de-France Region 75018

France

Heidelberg University Hospital, Clinic for Cardiology, Angiology and Pneum

Heidelberg, Baden-Wurttemberg 69120

Germany

LMU Klinikum - Medizinische Klinik und Poliklinik I

München, Bavaria 81377

Germany

Universitätsklinik Würzburg Deutsches Zentrum für Herzinsuffizienz

Würzburg, Bavaria 97078

Germany

Kerckhoff-Klinik GmbH

Bad Nauheim, Hesse 61231

Germany

Universitaetsklinikum Frankfurt, Med. Klinik III - Kardiologie, Angiologie

Frankfurt am Main, Hesse 60590

Germany

Asklepios Klinik Langen-Seligenstadt GmbH

Langen, Hesse 63225

Germany

Universitaetsmedizin Goettingen

Göttingen, Lower Saxony 37075

Germany

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia 53127

Germany

Uniklinikum Saarland

Homburg, Saarland 66424

Germany

Dr. med. Jens Taggeselle

Markkleeberg, Saxony 04416

Germany

Helios Klinikum Erfurt GmbH

Erfurt, 99089

Germany

UKE, Klinik fur Kardiologie

Hamburg, 20246

Germany

UKE, Klinik für Kardiologie

Hamburg, 20246

Germany

Universitaetsklinikum Jena

Jena, 07747

Germany

Marienhaus Klinikum Mainz GmbH

Mainz, 55131

Germany

General Hospital of Athens ''G. Gennimatas''

Athens, Attica 11527

Greece

General Hospital of Athens ''Hippokratio''

Athens, Attica 11527

Greece

General Hospital of Nea Ionia ''Konstantopouleio-Patision''

Athens, Attica 14233

Greece

University General Hospital ''ATTIKON'' - General Hospital of West Attica H

Chaïdári, Attica 12462

Greece

General Hospital ''Asklepieio Voulas''

Voula, Attica 16673

Greece

General Hospital of Chalkida

Chalcis, Euboea 34100

Greece

University General Hospital of Alexandroupolis

Alexandroupoli, Evros 68100

Greece

Papageorgiou General Hospital of Thessaloniki

Efkarpia, Thessaloniki 56403

Greece

AHEPA University General Hospital of Thessaloniki

Thessaloniki, Thessaloniki 54636

Greece

University General Hospital of Larissa

Larissa, 41110

Greece

ASST Spedali Civili di Brescia

Brescia, BS 25123

Italy

Ospedale Infermi

Rimini, Emilia-Romagna 47923

Italy

Ospedale di Arzignano

Arzignano, Lombardy 36071

Italy

ASST Papa Giovanni XXIII

Bergamo, Lombardy 24127

Italy

Centro Cardiologico Monzino

Milan, Lombardy 20138

Italy

IRCCS Multimedica

Sesto San Giovanni, Lombardy 20099

Italy

IRCCS Ospedale San Raffaele

Milan, MI 20132

Italy

A.O. Perugia - Ospedale S.Maria della Misericordia

Perugia, Province Of Perugia 06129

Italy

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna

Cona, 44124

Italy

IRCCS San Raffaele

Roma, 00163

Italy

Balsammedica Sp. z o.o.

Warsaw, Masovian Voivodeship 01249

Poland

Centralny Szpital Kliniczny UCK WUM

Warsaw, Masovian Voivodeship 02-097

Poland

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15276

Poland

Krakowski Szpital Specjalistyczny im. Sw. Jana Pawla II

Krakow, 31202

Poland

SPZOZ Uniwersytecki Szpital Kliniczny nr 2 UM w Lodzi

Lodz, 90549

Poland

SPZOZ Centralny Szpital Kliniczny UM w Lodzi

Lodz, 92213

Poland

Szpital Sw. Anny w Miechowie

Miechów, 32200

Poland

Uniwersytecki Szpital Kliniczny w Opolu

Opole, 45401

Poland

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 61848

Poland

Poradnia AKA-MED Centrum Sp. z o.o.

Ruda Śląska, 41710

Poland

Tomasz Blicharski Lubelskie Centrum Diagnostyczne

Świdnik, 21040

Poland

Wojewodzki Szpital Zespolony im. L. Rydygiera

Torun, 87100

Poland

Hospital Clinico Universitario de Santiago

Santiago de Compostela, A Coruña 15706

Spain

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona 08907

Spain

Hospital San Juan de la Cruz

Úbeda, Jaen 23400

Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid 28222

Spain

Hospital Universitario Virgen de La Arrixaca

El Palmar, Murcia 30120

Spain

CHUVI - H.U. Alvaro Cunqueiro

Vigo, Pontevedra 36312

Spain

Hospital Universitario A Coruña

A Coruña, 15006

Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital Universitario Lucus Augusti

Lugo, 27003

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital Universitario de Salamanca

Salamanca, 37007

Spain

Hospital Universitario Virgen del Rocío

Seville, 41013

Spain

Hospital Universitari Joan XXIII de Tarragona

Tarragona, 43005

Spain

Hospital Clínico Universitario de Valencia

Valencia, 46010

Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026

Spain

Harefield Hospital

Harefield, Greater London UB96JH

United Kingdom

Southampton General Hospital

Southampton, Hampshire SO166YD

United Kingdom

Queen Elizabeth University Hospital

Glasgow, Scotland G514TF

United Kingdom

Basingstoke and North Hampshire Hospital

Basingstoke, RG249NA

United Kingdom

Castle Hill Hospital

Cottingham, HU165JQ

United Kingdom

Russells Hall Hospital

Dudley, DY12HQ

United Kingdom

Ulster Hospital

Dundonald, BT161RH

United Kingdom

Glasgow Royal Infirmary

Glasgow, G40SF

United Kingdom

Great Western Hospitals

Swindon, SN36BB

United Kingdom