Clinical trial NCT03759392: Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure With Reduced Ejection Fraction and Decreased Exercise Tolerance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure With Reduced Ejection Fraction
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2018-11-30
Enrollment: 276
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 purpose of this study is to evaluate the effect of treatment with omecamtiv mecarbil compared with placebo on exercise capacity as determined by cardiopulmonary exercise testing following 20 weeks of treatment with omecamtiv mecarbil or placebo

Detailed description: Oversight Authorities:

United States: Food and Drug Administration Canada: Health Canada France: National Agency for the Safety of Medicine and Health Products Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy and Nutrition Italy: Italian Medicines Agency Netherlands: Medicines Evaluation Board Poland: Chief Pharmaceutical Inspectorate Sweden: Medical Products Agency

Eligibility criteria: Inclusion Criteria

* Male or female, greater than or equal to 18 to lesser than or equal to 85 years of age
* History of chronic HF, defined as requiring continuous treatment with medications for HF for a minimum of 3 months before screening
* New York Heart Association (NYHA) class II or III at screening
* Left ventricular ejection fraction less than or equal to 35%
* On maximally tolerated HF standard of care (SoC) therapies consistent with regional clinical practice guidelines, if not contraindicated and according to investigator judgment of the subject's clinical status. Beta blocker dose must be stable for 30 days prior to randomization.
* N-terminal (NT)-proBNP level greater than or equal to 200 pg/mL
* Peak VO2 less than or equal to 75% of the predicted normal value with respiratory exchange ratio (RER) greater than or equal to 1.05 on a screening CPET, confirmed by a CPET core laboratory

Exclusion Criteria

* Severe uncorrected valvular heart disease
* Paroxysmal atrial fibrillation or flutter documented within the previous 6 months, direct-current (DC) cardioversion or ablation procedure for atrial fibrillation within 6 months, or plan to attempt to restore sinus rhythm within 6 months of randomization. Subjects with persistent atrial fibrillation and no sinus rhythm documented in the prior 6 months are permitted.
* Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart block without a pacemaker.
* History of gastrointestinal bleeding requiring hospitalization, urgent procedure or transfusion in the prior year, or received intravenous (IV) iron, blood transfusion, or an erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or planned blood transfusion or ESA use during the study screening or treatment period. Chronic, stable use of oral iron is permitted.
* Ongoing or planned enrollment in cardiac rehabilitation.
* Requires assistance to walk or use of mobility assistive devices such as motorized devices, wheelchairs, or walkers. The use of canes for stability while ambulating is acceptable if the subject is deemed capable of performing CPET.
* Major medical event or procedure within 3 months prior to randomization, including: hospitalization, surgery, renal replacement therapy or cardiac procedure. This includes episodes of decompensated HF that require IV HF treatment.
* At screening: Resting systolic BP greater than 140 mmHg or less than 85 mmHg, or diastolic BP greater than 90 mmHg (mean of triplicate readings); Resting heart rate greater than 90 beats per minute, or less than 50 beats per minute (mean of triplicate readings); Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 (by the modified Modification of Diet in Renal Disease equation); Hepatic impairment defined by a total bilirubin (TBL) greater than or equal to 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times ULN. Patients with documented Gilbert syndrome and TBL greater than or equal to 2 times ULN due to unconjugated hyperbilirubinemia, without other hepatic impairment, are permitted.
* Room air oxygen saturation under 90% at screening
* Hemoglobin less than 10.0 g/dL at screening
* Significant adverse finding (e.g., exercise-induced early ischemic changes, abnormal decrease in BP \[systolic BP falls by more than 10 mmHg\], unexpected arrhythmia or other serious finding) during CPET at screening that precludes safe participation in the study, per investigator
* Chronotropic incompetence (including inadequate pacemaker rate response) during CPET at screening, defined as a maximum heart rate \<60% of the maximum predicted heart rate

Primary outcomes:
measure: Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20
timeFrame: Baseline and Week 20
Secondary outcomes:
measure: Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20
timeFrame: Baseline and Week 20
measure: Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20
timeFrame: Baseline and Week 20
measure: Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20
timeFrame: Baseline (Week -2 to Day 1) to Weeks 18-20
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Heart and Vascular Institute
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Cardiology Clinic
state: Arkansas
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates, PC
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital-University of Connecticut School of Medicine
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital - Fort Lauderdale
state: Florida
city: Pembroke Pines
country: United States
facility: Broward Research Center - Pembroke Pines
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Community Hospital South, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Medical Group Inc.
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) - Cardiac Unit Associates
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Heart & Vascular Institute
state: Michigan
city: Petoskey
country: United States
facility: McLaren Health Care Corporation
state: Michigan
city: Ypsilanti
country: United States
facility: Michigan Heart
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Health System
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Research Institute, Cardiology
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Elmer
country: United States
facility: Cardiovascular Associates Of The Delaware Valley (Cadv), P.A. - Elmer Physicians Care Center - Elmer
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Rosedale
country: United States
facility: Queens Heart Institute
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Med Health and Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Tulsa
country: United States
facility: St. John Clinical Research Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health
state: Oregon
city: Camp Hill
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster Heart And Stroke Foundation
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Dallas
country: United States
facility: University of Texas - Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Heart and Vascular Hospital
state: Texas
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre - University Hospital
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Universite de Montreal Institut de Cardiologie de Montreal ICM Montreal Heart Institute MHI
state: Quebec
city: Montreal
country: Canada
facility: Mcgill University Health Centre (MUHC)-The Montreal General Hospital (MGH)
state: Quebec
city: Bayonne cedex
country: France
facility: Centre Hospitalier De La Cote Basque
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste de Grenoble
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble-Hopital Albert Michallon
city: Nantes CEDEX 1
country: France
facility: Universite De Nantes - L'Institut Du Thorax
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Lariboisiere
city: Rouen Cedex
country: France
facility: Chu de Rouen Hopital Charles Nicolle
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil
city: Heidelberg
country: Germany
facility: Universitaetsklinik Heidelberg
state: Baden-wurttemberg
city: Magdeburg
country: Germany
facility: Universitatsklinikum Magdeburg
state: Saxony-Anhalt
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
state: Thueringen
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik- Bad Nauheim
city: Dresden
country: Germany
facility: Praxisklinik Dresden
city: Homburg
country: Germany
facility: Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes
city: Balatonfured
country: Hungary
facility: Balatonfuredi Allami Szivkorhaz
city: Budapest
country: Hungary
facility: Semmelweis University Heart and Vascular Center
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)
city: Foggia
country: Italy
facility: Ospedali Riuniti Foggia
state: Apulia
city: Milano
country: Italy
facility: Centro Cardiologico Monzino IRCCS
state: Lombardia
city: Bologna
country: Italy
facility: Azienda Ospedaliera S.Orsola Malpighi
state: Province Of Bologna
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
state: Province Of Brescia
city: Roma
country: Italy
facility: Insituto Di Ricovero E Cura A Carattere Scientifico San Raffaele Pisana
state: Rome
city: Napoli
country: Italy
facility: Divisione di Cardiologia con Utic ed Emodinamica
city: Napoli
country: Italy
facility: Ospedale Monaldi
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Universitair Medisch Centrum Rotterdam
state: South Holland
city: 'S-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis (OLVG) Locatie West
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
city: Nijmegen
country: Netherlands
facility: Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc)
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht - Wilhelmina Kinderziekenhuis
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum Veldhoven
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk Sp z o.o. Sp. k.
state: Podkarpackie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Kliniczne Centrum Kardiologii
city: Krakow
country: Poland
facility: Oddzial Kliniczny Choroby Wiencowej i Niewydolnosci Serca z Pododdzialem Intensywnego Nadzoru Kardiologicznego
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika, Oddzial Kardiologiczny
city: Warsaw
country: Poland
facility: Instytut Kardiologii Heart Failure Clinic
city: Wroclaw
country: Poland
facility: Centrum Chorob Serca, Uniwersytecki Szpital Kllniczny im. Jana Mikulicza Radeckiego we Wrociawiu
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Lund
country: Sweden
facility: Enhet Klinisk forskning, hjartmedicin, Skanes Universitet Sjukhus
Study officials:
affiliation: Cytokinetics
name: Cytokinetics, MD
role: STUDY_DIRECTOR
References:
citation: Lewis GD, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, Ezekowitz JA, Bohm M, Teerlink JR, Docherty KF, Lopes RD, Divanji PH, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Felker GM. Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure With Reduced Ejection Fraction: The METEORIC-HF Randomized Clinical Trial. JAMA. 2022 Jul 19;328(3):259-269. doi: 10.1001/jama.2022.11016.
citation: Lewis GD, Docherty KF, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, Ezekowitz JA, Ponikowski P, Bohm M, Teerlink JR, Heitner SB, Kupfer S, Malik FI, Meng L, Felker GM. Developments in Exercise Capacity Assessment in Heart Failure Clinical Trials and the Rationale for the Design of METEORIC-HF. Circ Heart Fail. 2022 May;15(5):e008970. doi: 10.1161/CIRCHEARTFAILURE.121.008970. Epub 2022 Mar 3.