Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity (Events Indicating Disease Worsening) & Mortality (Death Rate) in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%

Heart Failure Clinical Trial

— FINEARTS-HF  

Official title:

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity and Mortality in Participants With Heart Failure (NYHA II-IV) and Left Ventricular Ejection Fraction ≥ 40% (LVEF ≥ 40%)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04435626
• Other study ID #: 20103
• Secondary ID: 2020-000306-29
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 14, 2020
• Est. completion date: June 5, 2024

Study information

• Verified date: May 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of finerenone compared to placebo (a tablet without active substance) in the reduction of cardiovascular death (generally meaning death due to disease of the heart or blood vessels) and total Heart Failure (HF) events, including HF hospitalization and urgent visits for HF(generally meaning a hospital stay or urgent presentation to a healthcare unit due to worsening symptoms of heart failure) in patients suffering from HF with an ejection fraction greater than or equal to 40%. Researchers will also collect information on how much the heart disease has impact on patient's lives, change of kidney function, and how well finerenone treatment is tolerated. The study plans to enroll 6000 male and female patients of the age of 40 years and above suffering from heart failure with ejection fraction greater than or equal to 40%. Participants will take the study product as oral tablet with a dose between 0 (Placebo) 40 mg once daily. Study duration will be up to 43 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6016
• Est. completion date: June 5, 2024
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Participant (male or female) must be aged 40 years and older.

• Diagnosis of heart failure with New York Heart Association(NYHA) class II-IV, ambulatory or hospitalized primarily for heart failure.

• On diuretic treatment for at least 30 days prior to randomization.

• Documented left ventricular ejection fraction (LVEF) of =40% measured by any modality within the last 12 months.

• Structural heart abnormalities based on any local imaging measurement within the last 12 months, defined by at least one of the following findings: left atrial diameter (LAD) =3.8cm, left atrial area (LAA) =20cm2, left atrial volume index (LAVI) >30 mL/m2, left ventricular mass index (LVMI) =115 g/m2 (?)/ 95 g/m2 (?), septal thickness or posterior wall thickness =1.1 cm

• n-terminal prohormone B-type natriuretic peptide (NT-proBNP) =300 pg/mL (BNP =100 pg/mL) in sinus rhythm and patient does not have an ongoing diagnosis of paroxysmal atrial fibrillation or NT-proBNP =900 pg/mL (BNP =300 pg/mL) in atrial fibrillation (or if atrial fibrillation status is unknown or if patient has an ongoing diagnosis of paroxysmal atrial fibrillation) for participants obtained at the following time:

• Within 90 days prior to randomization if patient had been hospitalized for heart failure (HF) requiring initiation or change in HF therapy or if patient had an urgent visit for HF requiring intravenous (IV) diuretic therapy, both within 90 days prior to randomization OR

• Within 30 days prior to randomization if patient has not been hospitalized for HF nor had an urgent HF visit within the past 90 days.

• Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and baseline and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for those participating in clinical trials.

Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m² at either screening or randomization visit.

• Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit.

• Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to randomization

• Myocardial infarction or any event which could have reduced the ejection fraction within 90 days prior to randomization

• Coronary artery bypass graft surgery in the 90 days prior to randomization

• Percutaneous coronary intervention in the 30 days prior to randomization

• Stroke or transient ischemic cerebral attack within 90 days prior to randomization

• Probable alternative cause of participants' HF symptoms that in the opinion of the investigator primarily accounts for patient's dyspnea such as significant pulmonary disease, anemia or obesity. Specifically, patients with the below are excluded: Severe pulmonary disease requiring home oxygen, or chronic oral steroid therapy, History of primary pulmonary arterial hypertension, Hemoglobin <10 g/dl, Valvular heart disease considered by the investigator to be clinically significant, Body Mass Index (BMI) >50 kg/m2 at screening

• Systolic blood pressure(SBP) =160 mmHg if not on treatment with =3 blood pressure lowering medications or =180 mmHg irrespective of treatments, on 2 consecutive measurements at least 2-minute apart, at screening or at randomization.

• Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin) or moderate or potent CYP3A4 inducers, that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Finerenone (BAY94-8862)
For participants with an eGFR =60 mL/min/1.73 m^2: Starting dose is 10 mg OD and maximum dose 20 mg OD. For participants with an eGFR >60 mL/min/1.73 m^2: Starting dose is 20 mg OD and maximum dose 40 mg OD. Finerenone is administered orally as immediate release tablets.

Other:
• Placebo
Placebo tablets matching BAY94-8862 are administered orally.

Locations

Country	Name	City	State
Argentina	Centro de Investigaciones Metabólicas	Buenos Aires	Ciudad Auton. De Buenos Aires
Argentina	Hospital Militar Central "CIR. MY. C. Argerich"	Buenos Aires	Ciudad Auton. De Buenos Aires
Argentina	Instituto Cardiovascular de Buenos Aires - Buenos Aires, Argentina	Buenos Aires	Ciudad Auton. De Buenos Aires
Argentina	Centro de Investigaciones Clínicas	Caba	Ciudad Auton. De Buenos Aires
Argentina	IMOBA Investigaciones Clinicas	Caba	Buenos Aires
Argentina	Clínica Privada del Prado	Córdoba
Argentina	Instituto Médico DAMIC- Fundación Rusculleda	Córdoba
Argentina	Clínica Coronel Suarez	Coronel Suarez	Buenos Aires
Argentina	Inst. de Cardiología de Corrientes Juana Francisca Cabral	Corrientes
Argentina	Hospital Italiano de La Plata | Clinical Research Department	La Plata	Buenos Aires
Argentina	Centro de Investigaciones Medicas Lanus | Research Department	Lanus	Buenos Aires
Argentina	Sanatorio Modelo Quilmes	Quilmes	Buenos Aires
Argentina	Instituto Cardiovascular	Rosario	Santa Fe
Argentina	Instituto Médico de la Fundación Estudios Clinicos	Rosario	Santa Fe
Argentina	Corporación Médica de General San Martín	San Martín	Buenos Aires
Argentina	Instituto de Cardiologia | Tucuman, AR	San Miguel de Tucuman	Tucuman
Argentina	Centro de Investigaciones Clinicas del Litoral	Santa Fe
Argentina	Centro de Especialidades Médicas	Villa Luro	Ciudad Auton. De Buenos Aires
Argentina	Instituto de Investigaciones Clínicas Zárate	Zárate	Buenos Aires
Australia	The Wesley Hospital	Auchenflower	Queensland
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Advara HeartCare Ringwood	Bundoora	Victoria
Australia	The Prince Charles Hospital	Chermside
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Advara HeartCare Leabrook	Leabrook	South Australia
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Austria	Krankenhaus St. Josef Braunau	Braunau	Oberösterreich
Austria	Landeskrankenhaus Feldkirch	Feldkirch	Vorarlberg
Austria	Medizinische Universität Graz	Graz	Steiermark
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt	Kärnten
Austria	Uniklinikum Salzburg - Landeskrankenhaus	Salzburg
Austria	Universitätsklinikum St. Pölten	St. Pölten	Niederösterreich
Austria	Imed19-privat	Wien
Austria	Klinik Floridsdorf - Krankenhaus Nord	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Brazil	Centro de Pesquisa Clinica do Coração | Aracaju, Brasil	Aracaju	Sergipe
Brazil	Hospital Felício Rocho	Belo Horizonte	Sao Paulo
Brazil	MK Consultoria Médico Científica Ltda/Angiocor Blumenau	Blumenau	Santa Catarina
Brazil	Hospital do Coração do Brasil	Brasilia	Distrito Federal
Brazil	Campinas Clinical Research Institute (IPECC) | Campinas, Brazil	Campinas	Sao Paulo
Brazil	Hospital PUC-Campinas | Centro de Pesquisa Clínica Sao Lucas	Campinas
Brazil	Fundação Universidade de Caxias do Sul	Caxias do Sul	Rio Grande Do Sul
Brazil	QUANTA Diagnósticos e Terapia	Curitiba	Parana
Brazil	Hospital das Clínicas de Goiânia	Goiânia	Goiás
Brazil	Instituto do Coração de Marilia | Marilia, Brasil	Marília	Sao Paulo
Brazil	Eurolatino Pesquisas Medicas | Uberlandia, MG	Minas Gerais
Brazil	Sociedade Hospitalar Angelina Caron | Departamento de Ensino e Pesquisa	Paraná	Parana
Brazil	Hospital de Clinicas de Porto Alegre | Clinical Research Center - Surgery Research Center	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Mae de Deus	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceição	Porto Alegre	Rio Grande Do Sul
Brazil	Centro Avançado de Pesquisa para Diagnóstico - CAPED	Ribeirão Preto	Sao Paulo
Brazil	Santa Casa de Misericórdia da Bahia	Salvador	Bahia
Brazil	IMC - Instituto de Moléstias Cardiovasculares Tatui	Tatui	Sao Paulo
Brazil	Santa Casa de Misericórdia de Votuporanga	Votuporanga	Sao Paulo
Bulgaria	Ambulatory facility for specialized outpatient medical care	Burgas
Bulgaria	MHAT Haskovo	Haskovo
Bulgaria	MHAT Zdrave	Pazardjik
Bulgaria	¿ultidisc. hosp. for act. treatm. Sveti Georgi - Pernik OOD	Pernik
Bulgaria	Medical Center Medconsult Pleven	Pleven
Bulgaria	Medical centre Hipokrat - N EOOD	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment Medline | Cardiology Department	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment Sveta Karidad | Cardiology Department	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment | Shumen - First Department of Internal Medicine	Shumen
Bulgaria	MHAT Hadzhi Dimitar	Sliven
Bulgaria	Medical Center Hera	Sofia
Bulgaria	MHAT National Cardiology Hospital EAD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment Knyaginya Klementina Sofia EAD | Cardiology Department	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment Sveta Sofia | Internal Diseases Department	Sofia
Bulgaria	NMTH Tzar Boris III	Sofia
Bulgaria	Second Medical Center Sofia EOOD	Sofia
Bulgaria	UMHAT Tsaritsa Joanna-ISUL EAD Sofia	Sofia
Bulgaria	MHAT Trakia	Stara Zagora
Bulgaria	Multiprofile Hospital for Active Treatment Dr. Stefan Cherkezov | Cardiology Department	Veliko Tarnovo
Bulgaria	Multiprofile Hospital for Active Treatment Sveti Panteleymon Yambol | Cardiology Department	Yambol
Canada	Brampton Clinical Trials	Brampton	Ontario
Canada	Cambridge Cardiac Care Center	Cambridge	Ontario
Canada	Vizel Cardiac Research	Cambridge	Ontario
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Centre intégré de santé et de services sociaux de Laval, Hôp	Laval	Quebec
Canada	London Health Sciences Centre	London	Ontario
Canada	KMH Cardiology Clinics Inc.	Mississauga	Ontario
Canada	G.A. Research Associates, Ltd.	Moncton	New Brunswick
Canada	Centre Hospitalier de l'Université de Montréal-CHUM	Montreal	Quebec
Canada	Clinique Sante Cardio MC	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Fraser Clinical Trials, Inc.	New Westminster	British Columbia
Canada	North York Diagnostic and Cardiac Centre	North York	Ontario
Canada	Oakville Cardiovascular Research	Oakville	Ontario
Canada	Office of Dr. James Cha, MD	Oshawa	Ontario
Canada	Kawartha Cardiology Clinical Trials	Peterborough	Ontario
Canada	Corcare	Scarborough	Ontario
Canada	Medicus MFC Inc.	Toronto	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Women's College Hospital	Toronto	Ontario
Canada	St. Boniface Hospital	Winnipeg	Manitoba
China	Beijing Anzhen Hospital, Capital Medical University	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing
China	Jilin Province People's Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Changsha Central Hospital	Changsha	Hunan
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos	Chengdu	Sichuan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hosp. Sun Yat-Sen Univ.	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou University of TCM	Guangzhou	Guangdong
China	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	Hainan Provincial People's Hospital	Haikou	Hainan
China	1st Affiliated Hospital of College Medicine, Zhejiang Univ.	Hangzhou	Zhejiang
China	Huai'an First People's Hospital, Nanjing Medical University	Huai'An	Jiangsu
China	Jinan Central Hospital	Jinan	Shandong
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	The First People's Hospital of Lianyungang	Lianyungang	Jiangsu
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Jiangning Hospital	Nanjing	Jiangsu
China	NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Nanjing Medical university	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Panjin Liaohe Oilfield Gem Flower Hospital	Panjin	Liaoning
China	Hainan Third People's Hospital (Province Nongken Sanya Hopt)	Sanya	Hainan
China	Shanghai East Hospital Affiated to Tongji University	Shanghai
China	Shanghai Tongji Hospital of Tongji University	Shanghai
China	The First Hospital of Hebei Medical Univesity	Shijiazhuang	Hebei
China	1st Affiliated hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin People's Hospital	Tianjin
China	People's Hospital of Xinjiang Uygur Autonomous Region	Urumqi	Xinjiang
China	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Shanxi Provincial People's Hospital	XI 'an	Shanxi
China	Shaanxi Provincial People's Hospital	Xi'an	Shanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Xinxiang Central Hospital	Xinxiang	Henan
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Yinchuan No.1 People's Hospital	Yinchuan	Ningxia
Colombia	Fundación Cardiomet CEQUIN Eje Cafetero	Armenia	Quindío
Colombia	Clínica de la Costa SAS	Baranquilla	Atlántico
Colombia	Corazón IPS S.A.S.	Barranquilla	Atlántico
Colombia	Fundacio del Caribe para la Investigacio Bio-Medica (BIOS)	Barranquilla
Colombia	IPS Centro Cientifico Asistencial S.A.S	Barranquilla	Atlántico
Colombia	Caja de Compensación Familiar CAFAM	Bogota	Distrito Capital De Bogotá
Colombia	Fundación Cardioinfantil	Bogota
Colombia	Hospital Universitario Clínica San Rafael	Bogota
Colombia	Instituto del Corazón de Bucaramanga	Bucaramanga	Santander
Colombia	Clínica Imbanaco S.A.S	Cali	Valle Del Cauca
Colombia	Mediservis del Tolima IPS S.A.S	Ibague	Tolima
Colombia	Clinica Cardio VID	Medellin
Colombia	Hospital General de Medellin	Medellin	Antioquia
Colombia	Hospital San Vicente Fundación	Medellin
Colombia	Rodrigo Botero S.A.S	Medellin	Antioquia
Colombia	Hospital Alma Mater de Antioquia	Medellín	Antioquia
Colombia	Sociedad Médica Rionegro SOMER S.A.	Rionegro	Antioquia
Colombia	Hospital Universitario de San Ignacio	Santa Fe De Bogotá
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Kardiologicka ambulance Brno s.r.o.	Brno
Czechia	Kardiologie MUDr. Libor Nechvatal s.r.o.	Brno
Czechia	Kardiologicka ambulance	Cesky Krumlov
Czechia	Kardio Chlumec s.r.o.- Kardiologicka ambulance	Chlumec nad Cidlinou
Czechia	Poliklinika Dolni Brezany	Dolni Brezany
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec kralove
Czechia	Kromerizska nemocnice a.s.	Kromeriz
Czechia	LUNACOR, Centrum pro choroby srdce a cev	Kromeriz
Czechia	Krajska Nemocnice Liberec	Liberec
Czechia	KardioBusak s.r.o.	Louny
Czechia	Kardiologicka a interni ambulance	Pisek
Czechia	Fakultni nemocnice Plzen	Plzen
Czechia	Polabska zdravotni, s.r.o.	Podebrady
Czechia	Affidea Praha s.r.o	Praha 11 - Chodov
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Institut Klinicke a Experimentalni Mediciny	Praha 4
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Ustredni vojenska nemocnice Praha	Praha 6
Czechia	Kardio s.r.o.	Trebic
Czechia	Nemocnice Podlesi	Trinec
Czechia	Angiocor s.r.o.	Zlin
Czechia	Nemocnice Znojmo	Znojmo
Denmark	Aarhus Universitetshospital, Skejby	Aarhus N
Denmark	Sydvestjysk Sygehus Esbjerg | Kardiologisk Forskningsenhed	Esbjerg
Denmark	Capital Region | Gentofte Hospital - Cardiology Research	Hellerup
Denmark	Capital Region | Herlev Hospital - Department of Heart Disease	Herlev
Denmark	Region Midtjylland | Regionshospitalet Godstrup - Clinic for Heart Research	Herning
Denmark	Holbæk Sygehus	Holbæk
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Regionshospitalet Randers	Randers
Denmark	Odense University Hospital | Svendborg Hospital - Cardiovascular Research Unit	Svendborg
Finland	HUS Jorvin sairaala	Espoo
Finland	Tampereen yliopistollinen sairaala, keskussairaala	Tampere
Finland	Turun yliopistollinen keskussairaala	Turku
Germany	Städt. Kliniken Bielefeld gGmbH	Bielefeld	Nordrhein-Westfalen
Germany	Medizinische Hochschule Hannover (MHH)	Hannover	Niedersachsen
Germany	Sana-Klinikum Remscheid GmbH	Remscheid	Nordrhein-Westfalen
Germany	Herzklinik Ulm GbR	Ulm	Baden-Württemberg
Germany	Forschungszentrum Ruhr - KliFoCenter GmbH	Witten	Nordrhein-Westfalen
Germany	Klinikum der Universität Würzburg	Würzburg	Bayern
Greece	University General Hospital of Alexandroupolis	Alexandroupoli
Greece	General Hosp of Athens "Korgialenio-Benakeio" RCH	Ampelokipi - Athens
Greece	G. GENNIMATAS General State Hospital of Athens	Athens
Greece	General Hospital of Athens "ALEXANDRA"	Athens
Greece	HIPPOKRATION General Hospital of Athens	Athens
Greece	University General Hospital ATTIKON	Chaidari
Greece	University General Hospital of Heraklion	Heraklion
Greece	KAT General Hospital of Athens	Kifisia / Athens	Attica
Greece	University General Hospital of Larissa	Larissa
Greece	Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA	Nea Ionia / Athens
Greece	University General Hospital of Patra	Patra
Greece	Hippokration General Hospital of Thessaloniki	Thessaloniki
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Queen Elizabeth Hospital Hong Kong	Kowloon
Hong Kong	Princess Margaret Hospital	Lai Chi Kok
Hong Kong	Prince of Wales Hospital	Shatin	N.T
Hungary	Cardiomobile Egeszsegugyi Szolgaltato Kft.	Balatonfured
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Budapesti Jahn Ferenc Del-pesti Korhaz es Rendelointezet	Budapest
Hungary	Budapesti Uzsoki Utcai Korhaz	Budapest
Hungary	Eszak-Pesti Centrumkorhaz-Honvedkorhaz	Budapest
Hungary	University of Semmelweis/ Semmelweis Egyetem	Budapest
Hungary	University of Semmelweis/ Semmelweis Egyetem	Budapest
Hungary	Bugat Pal Korhaz	Gyongyos
Hungary	Pharma4Trial Kft.	Gyongyos
Hungary	Csongrad-Csanad Varmegyei Egeszsegugyi Ellato Kozpont Hodmezovasarhelyi Tagintezmeny	Hodmezovasarhely
Hungary	Borsod-Abauj-Zemplen Varmegyei Korhaz es Egyetemi Oktatokorhaz	Miskolc
Hungary	Nagykanizsai Kanizsai Dorottya Korhaz	Nagykanizsa
Hungary	Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.	Nyiregyhaza
Hungary	Coromed Smo Kft	Pecs
Hungary	Da Vinci Maganklinika	Pecs
Hungary	SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont	Szeged
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Tolna Varmegyei Balassa Janos Korhaz	Szekszard
Hungary	Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz	Szentes
India	Madras Medical Mission Institute	Chennai	Tamil Nadu
India	Max Super Speciality Hospital, Saket	New Delhi	Delhi
India	Safdarjung Hospital	New Delhi	Delhi
India	Deenanath Mangeshkar Hospital	Pune	Maharashtra
India	KEM hospital	Pune	Maharashtra
Israel	Assuta Ashdod	Ashdod
Israel	Barzilai Ashkelon University Medical Center | Cardiology Department	Ashkelon
Israel	Bnai Zion Medical Center	Haifa
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Corporation	Haifa
Israel	Hadassah Hebrew University Hospital Ein Kerem	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Poriya Medical Center | Cardiology Department	Lower Galilee
Israel	Health Corporation of Galilee Medical Center	Nahariya
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Health Corporation of the Ziv Medical Center (R.A.)	Zefat
Israel	Shamir Medical Center (Assaf Harofeh)	Zrifin
Italy	AUSL Toscana Sud-Est	Arezzo	Toscana
Italy	ASST Papa Giovanni XXIII	Bergamo	Lombardia
Italy	A.O.U. di Bologna Policlinico S.Orsola Malpighi	Bologna	Emilia-Romagna
Italy	AUSL di Bologna	Bologna	Emilia-Romagna
Italy	ASST del Garda	Brescia	Lombardia
Italy	ASST Spedali Civili di Brescia	Brescia	Lombardia
Italy	A.O.U. Mater Domini	Catanzaro	Calabria
Italy	ASST di Cremona	Cremona	Lombardia
Italy	A.O.U. di Ferrara	Ferrara	Emilia-Romagna
Italy	IRCCS Centro Cardiologico Monzino	Milano	Lombardia
Italy	IRCCS Istituti Clinici Scientifici Maugeri SpA SB	Milano	Lombardia
Italy	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Italy	ASST della Brianza	Monza Brianza	Lombardia
Italy	ASST di Monza	Monza Brianza	Lombardia
Italy	A.O.U. Policlinico Federico II Napoli	Napoli	Campania
Italy	A.O.U. Maggiore della Carità	Novara	Piemonte
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia	Lombardia
Italy	A.O. di Perugia	Perugia	Umbria
Italy	AUSL di Piacenza	Piacenza	Emilia-Romagna
Italy	A.O.U. Senese	Siena	Toscana
Italy	ASST Sette Laghi	Varese	Lombardia
Italy	A.O.U.I. Verona	Verona	Veneto
Japan	Nishiarai Heart Central Clinic	Adachi-ku	Tokyo
Japan	Ageo Central General Hospital	Ageo	Saitama
Japan	Japan Red Cross Society Azumino Hospital	Azumino	Nagano
Japan	Fukuoka University Nishijin Hospital	Fukuoka
Japan	Funabashi Municipal Medical Center	Funabashi	Chiba
Japan	Gifu Prefectural General Medical Center	Gifu
Japan	Minamino Cardiovascular Hospital	Hachioji	Tokyo
Japan	Public Central Hospital of Matto Ishikawa | Clinical Trial Management Office	Hakusan	Ishikawa
Japan	National Hospital Organization Hamada Medical Center	Hamada	Shimane
Japan	Hyogo Brain and Heart Center	Himeji	Hyogo
Japan	National Hospital Organization Iwakuni Clinical Center	Iwakuni	Yamaguchi
Japan	National Hospital Organization Kanazawa Medical Center | Clinical Trial Management Office	Kanazawa	Ishikawa
Japan	Mitoyo General Hospital | Kagawa, Japan	Kanonji	Kagawa
Japan	Kasugai Municipal Hospital	Kasugai	Aichi
Japan	Kawaguchi Cardiovascular and Respiratory Hospital	Kawaguchi	Saitama
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Steel Memorial Yawata Hospital	Kitakyushu	Fukuoka
Japan	National Hospital Organization Kobe Medical Center	Kobe	Hyogo
Japan	Kumamoto University Hospital	Kumamoto
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto
Japan	National Hospital Organization Tokyo Medical Center	Meguro-ku	Tokyo
Japan	Miyazaki Medical Association Hospital	Miyazaki
Japan	Iwate Prefectural Central Hospital	Morioka	Iwate
Japan	R.I.A.C Naha City Hospital	Naha	Okinawa
Japan	Shinrakuen Hospital	Niigata
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Japan	Oita Prefectural Hospital	Oita
Japan	The Sakakibara Heart Institute of Okayama	Okayama
Japan	Onga Nakama Medical Association Onga Hospital	Onga-gun	Fukuoka
Japan	Osaka General Medical Center	Osaka
Japan	Osaka Police Hospital | Clinical Research and Trial Center	Osaka
Japan	Social Corporation Keigakukai Minamiosaka Hospital	Osaka
Japan	Toho University Omori Medical Center	Ota-ku	Tokyo
Japan	Kitasato University Hospital	Sagamihara	Kanagawa
Japan	Sagamihara Kyodo Hospital	Sagamihara	Kanagawa
Japan	Saitama Sekishinkai Hospital	Sayama	Saitama
Japan	JCHO Shimonoseki Medical Center	Shimonoseki	Yamaguchi
Japan	Shobara Red Cross Hospital	Shobara	Hiroshima
Japan	Kagawa Prefectural Central Hospital	Takamatsu	Kagawa
Japan	Higashi Takarazuka Satoh Hospital	Takarazuka	Hyogo
Japan	Takatsuki Red Cross Hospital	Takatsuki	Osaka
Japan	JA Toride Medical Center	Toride	Ibaraki
Japan	Toyama University Hospital	Toyama
Japan	TOYOTA Memorial Hospital	Toyota	Aichi
Japan	National Hospital Organization Shinshu Ueda Medical Center	Ueda	Nagano
Japan	Seiyu Memorial Hospital	Wakayama
Japan	Japan Organization of Occupational Health and Safety Sanin Rosai Hospital	Yonago	Tottori
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang	Gyeonggido
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbugdo
Korea, Republic of	Chung Nam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Bundang Cha Hospital	Seongnam-si	Gyeonggido
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Yonsei University Wonju Christian Hospital	Wonju	Gang''weondo
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Jelgava Outpatient Clinic	Jelgava
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	1st Riga Clinical Hospital	Riga
Latvia	GK Neiroklinika	Riga
Latvia	P. Stradins Clinical University Hospital	Riga
Latvia	Gita Rancane - cardiology private practice	Ventspils
Lithuania	UAB "Klinikiniai sprendimai" Alytus	Alytus
Lithuania	LUHS Kauno Hospital (Josvainiu str.)	Kaunas
Lithuania	LUHS Kauno Hospital (Laisves ave.)	Kaunas
Lithuania	Saules family medicine center	Kaunas
Lithuania	Klaipedos Jurininku Ligonine	Klaipeda
Lithuania	Siauliai Republican hospital	Siauliai
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Malaysia	Gleneagles Penang Medical Center	George Town,
Malaysia	Institute Jantung Negara	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Raja Permaisuri Bainun	Perak
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Malaysia	Sarawak Heart Centre	Sarawak
Malaysia	Hospital Serdang	Selangor
Mexico	Hospital General de Acapulco	Acapulco	Guerrero
Mexico	Hospital Cardiologica Aguascalientes	Aguascalientes
Mexico	Hospital de Jesús	Alcaldía Cuauhtemoc	Distrito Federal
Mexico	Fundación de Atencion e Investigacion Medica Lindavista SC	Alcaldia Gustavo A. Madero	Distrito Federal
Mexico	Centro de Investigacion y Atencion Integral Durango S.C.	Durango
Mexico	Consultorio de Medicina Especializada del Sector Privado	Guadalajara	Jalisco
Mexico	Centro de Estudios Clinicos de Queretaro S. C. (CECLIQ)	Queretaro	Querétaro
Mexico	Centro de Investigación Médica Dr. Alberto Bazzoni SA de CV	Torreón	Coahuila
Mexico	Hospital Ángeles de Xalapa	Xalapa	Veracruz
Netherlands	Ziekenhuis Groep Twente	Almelo
Netherlands	Tergooiziekenhuizen-Blaricum	Blaricum
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Slingeland Ziekenhuis	Doetinchem
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Ziekenhuis St. Jansdal	Harderwijk
Netherlands	Maastricht UMC	Maastricht
Netherlands	Isala Meppel	Meppel
Netherlands	Antonius Ziekenhuis Sneek	Sneek
Netherlands	Maxima Medisch Centrum, locatie Veldhoven	Veldhoven
New Zealand	University of Auckland	Auckland
New Zealand	Christchurch Heart Institute	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	P3 Research Ltd Hawkes Bay	Hawkes Bay
New Zealand	Hutt Hospital	Lower Hutt
New Zealand	Nelson Hospital	Nelson
New Zealand	P3 Research	Tauranga
Poland	KLIMED Marek Klimkiewicz	Bialystok
Poland	MICS Centrum Medyczne Bydgoszcz	Bydgoszcz
Poland	Uniwersyteckie Centrum Medycyny Morskiej i Tropikalnej	Gdynia
Poland	Samodzielny Publiczny Specjalistyczny Szpital Zachodni	Grodzisk Mazowiecki
Poland	CLINICAL MEDICAL RESEARCH Sp. z o. o.	Katowice
Poland	Unicardia Specjalistyczne Centrum Leczenia Ch.Serca i Naczyn	Krakow
Poland	IMEDICA Centrum Medyczne	Lublin
Poland	NZOZ "Twoja Przychodnia" Sp. z o.o.	Lublin
Poland	Zechowicz Medeusz-Plus Lekarska Spolka Partnerska	Olsztyn
Poland	Oswiecimskie Centrum Badan Klinicznych Medicome Sp. z o.o.	Oswiecim
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan
Poland	Szpital Specjalistyczny SPZOZ	Pulawy
Poland	NZOZ Pro-Cordis Sopockie Centrum Badan Kardiologicznych	Sopot
Poland	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin
Poland	Gessek Jacek Prywatny Gabinet Lekarski	Torun
Portugal	Hospital Prof. Dr. Fernando Fonseca	Amadora
Portugal	BlueClinical | Centro Hospitalar Baixo Vouga - Unidade Aveiro - Gabinete de Ensaios Clinicos	Aveiro
Portugal	Centro Hospitalar e Universitario de Coimbra, E.P.E. | Department of Cardiology, Research Unit	Coimbra
Portugal	Centro Hospitalar Universitario Cova de Beira | Clinical Research Department	Covilha	Castelo Branco
Portugal	ULSG - Unidade Local de Saude da Guarda	Guarda
Portugal	Hospital da Senhora da Oliveira | Clinical Research Department	Guimaraes	Braga
Portugal	Centro Hospitalar de Leiria | Santo Andre Hospital - Research Center	Leiria
Portugal	Centro Hospitalar de Lisboa Ocidental | Clin Res Dept	Lisboa
Portugal	Luz Saude | Hospital da Luz Lisboa - Centro de Investigacao Clinica	Lisboa
Portugal	ULSM - Hospital Pedro Hispano	Matosinhos	Porto
Portugal	Centro Hospitalar Universitario do Porto	Porto
Portugal	Hospital da Luz - Setubal	Setubal	Setúbal
Romania	Sp. Judetean de Urgenta Dr. Constantin Opris Baia Mare	Baia Mare
Romania	Emergency County Hospital, Braila	Braila
Romania	S.C Thera Card S.R.L	Brasov
Romania	Emergency Institute for Cardiovascular Diseases	Bucharest
Romania	Spitatul Universitar de Urgenta Bucaresti	Bucharest
Romania	Emergency Institute for Cardiovascular Diseases	Bucuresti
Romania	Spitalul Clinic de Urgenta "Sf. Pantelimon"	Bucuresti
Romania	Emergency Clinical County Hospital Craiova	Craiova Dolj
Romania	Sf. Ap. Andrei Emergency Clinical County Hospital Galati	Galati
Romania	S.C. CARDIOMED S.R.L. Iasi	Iasi
Romania	S.C. Sal Med SRL	Pitesti
Romania	CMI. Dr. Podoleanu Cristian	Targu Mures	Mures
Romania	S.C. Cardio Med S.R.L.	Targu Mures
Romania	Municipal Clinical Emergency Hospital of Timisoara	Timisoara
Romania	Spitalul Clinic Municipal de Urgenta "Timisoara"	Timisoara	Timis
Romania	Timisoara Institute of Cardiovascular Diseases	Timisoara
Russian Federation	SBHI of Sverdlovsk Region Aramil City Hospital	Aramil
Russian Federation	First City Clinical Hospital n.a. E.E. Volosevich	Arkhangelsk
Russian Federation	Altai Regional Cardiological Dispensary	Barnaul
Russian Federation	SBEI "Chita State Medical Academy"	Chita
Russian Federation	Izhevsk City Clinical Hospital #9	Izhevsk
Russian Federation	Clinical Diagnostic Center	Kazan
Russian Federation	Kazan Federal University	Kazan
Russian Federation	Sci-Res. Institute of Complex Cardiovascular Disorders	Kemerovo
Russian Federation	Center of cardiology and neurology	Kirov
Russian Federation	City Clinical Hospital #51	Moscow
Russian Federation	City clinical hospital n.a. V.V. Vinogradov	Moscow
Russian Federation	Moscow State University n.a. M.V. Lomonosov	Moscow
Russian Federation	Research center of therapy and prophylactic medicine	Moscow
Russian Federation	Russian Clinical and Research Center of Gerontology	Moscow
Russian Federation	State Novosibirsk Regional Clinical Hospital	Novosibirsk
Russian Federation	Omsk Region "Clinical Health Unit No. 9"	Omsk
Russian Federation	Penza Regional Clinical Hospital n.a. N.N. Burdenko	Penza
Russian Federation	Perm Regional Hospital for War Veterans	Perm
Russian Federation	Rostov-on-Don Emergency Clinical Hospital	Rostov-on-Don
Russian Federation	SBI of the Ryazan region "Regional clinical hospital"	Ryazan
Russian Federation	Samara Regional Clinical Cardiology Dispensary n.a. Polyakov	Samara
Russian Federation	Clinical Hospital #3 n.a. S.R. Mirotvortsev	Saratov
Russian Federation	LLC Astarta	St. Petersburg
Russian Federation	Scien. Res. Inst. of Emergency Care n.a. I.I. Dzhanelidze	St. Petersburg
Russian Federation	St. Petersburg Clinical Hospital of RAS	St. Petersburg
Russian Federation	Scientific Research Institute of Cardiology	Tomsk
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Yekaterinburg
Slovakia	Stredoslovensky ustav srdcovych a cievnych chorob, a.s.	Banska Bystrica
Slovakia	ALIAN s.r.o.	Bardejov
Slovakia	Centrum interv. neuroradiologie a endovaskularnej liecby	Bratislava
Slovakia	Kardiosanus | Bratislava, Slovakia	Bratislava
Slovakia	Nemocnica svateho Michala, a.s.	Bratislava
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica Stare Mesto	Bratislava
Slovakia	Narodny ustav srdcovych a cievnych chorob, a.s	Bratislava 37
Slovakia	Nemocnica s poliklinikou Brezno, n.o.	Brezno
Slovakia	Dolnooravska nemocnica s poliklinikou L. Nadasi Jegeho	Dolny Kubin
Slovakia	JG-COR s.r.o.	Kosice
Slovakia	Medical Group Kosice s.r.o. | Kosice, Slovakia	Kosice
Slovakia	KARDIO-ANGIO s.r.o.	Levice
Slovakia	KardioMed s.r.o.	Lucenec
Slovakia	MEDI M&M, s.r.o.	Moldava nad Bodvou
Slovakia	Kardiocentrum Nitra | Cardiology Clinic - Outpatient Department	Nitra
Slovakia	KARDIOMED NZ s.r.o.	Nove Zamky
Slovakia	MEDISPOL s.r.o.	Presov
Slovakia	COR, s.r.o	Sahy
Slovakia	Medivasa s.r.o.	Zilina
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Santa María del Puerto	El Puerto de Santa María	Cádiz
Spain	Complejo Hospitalario Universitario de Ferrol | Hospital Naval - Unidad de Hipertensión Arterial	Ferrol	A Coruña
Spain	Hospital Universitario Virgen de las Nieves|Cardiologia	Granada
Spain	Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Dr. Negrín	Las Palmas de Gran Canaria	Las Palmas
Spain	Hospital Universitario Arnau de Vilanova de Lleida	Lleida
Spain	Hospital Ramón y Cajal | Medicina Interna	Madrid
Spain	Hospital Sanitas La Zarzuela | Cardiologia	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen de la Victoria | Cardiology Department	Malaga	Málaga
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital San Rafael	Salvador
Spain	Hospital del Servei Valencià de Salud de la Vega Baja	San Bartolomé	Alicante
Spain	Jose Manuel Pascual Pascual S.A. | Hospital Virgen del Camino - Internal Medicine Department	Sanlucar de Barrameda	Cádiz
Spain	Complejo Hospitalario Ntra. Sra. de Valme	Sevilla
Spain	Hospital Alta Resolucion de Utrera | Cardiology Service Department	Utrera	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital de Manises	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	La Fe University and Polytechnic Hospital | Cardiology Department	Valencia
Spain	Jose Manuel Pascual Pascual S.A. | Hospital Virgen de las Montanas - Internal Medicine Department	Villamartin	Cádiz
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Mackay Memorial Hospital - Hsinchu Branch	Hsinchu
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital at Linkou	Tao-Yuan
Turkey	Afyonkarahisar Saglik Bilimleri Universitesi	Afyonkarahisar
Turkey	Saglik Bilimleri Universitesi Antalya EA Hastanesi	Antalya
Turkey	Trakya Univ. Tip Fak.	Edirne
Turkey	Eskisehir Osmangazi Universitesi Tip Fakultesi	Eskisehir
Turkey	Istanbul Mehmet Akif Ersoy Gogus Kalp Damar Cerrahisi E.A.H.	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Istanbul Universitesi Kardiyoloji Enstitusu	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi	Izmir
Turkey	Erciyes Universitesi Tip Fakultesi	Kayseri
Turkey	Kocaeli Universitesi Tip Fakultesi	Kocaeli
Turkey	Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi	Konya
Turkey	Kutahya Saglik Bilimleri Uni. Evliya Celebi Egitim ve Arasti	Kutahya
Turkey	Mersin Universitesi Tip Fakultesi	Mersin
Ukraine	Cherkasy Regional Cardiological Center	Cherkasy
Ukraine	"Clinical Emergency Hospital" of Dnipro City Council	Dnipro
Ukraine	Miska Klinichna likarnya No 8	Kharkiv
Ukraine	National Institute of Therapy named after L.T.Maloyi	Kharkiv
Ukraine	Regional Dispensary of Radiation Protection of Population	Kharkiv
Ukraine	City Clinical Hospital # 1	Kiev
Ukraine	Institute of Cardiology AMS	Kiev
Ukraine	LLC Medical Centre CONSILIUM MEDICAL	Kyiv
Ukraine	Medbud-Clinic LLC	Kyiv
Ukraine	Railway Clinical Hospital #2	Kyiv
Ukraine	Lviv regional clinical medical & diagnostic cardiology cente	Lviv
Ukraine	Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi	Poltava
Ukraine	Zakarpatsky Oblasnyi Kardiologichnyi Dyspanser	Uzhgorod
Ukraine	Vinnytsia City Clinical Hospital #1	Vinnytsia
Ukraine	Regional Clinical Hospital - Vinnytsya	Vinnytsya
Ukraine	Regional medical center of cardio-vascular disease	Zaporizhzhja
Ukraine	Zaporizhia Municipal Clinical Hospital No.10	Zaporizhzhya
Ukraine	Zaporizhzhya City Emergency Care Hospital	Zaporizhzhya
Ukraine	Communal Institution Central City Hospital 1 of Zhytomyr	Zhytomyr
United Kingdom	Wansbeck General Hospital	Ashington	Northumberland
United Kingdom	North Hampshire Hospital	Basingstoke	Hampshire
United Kingdom	Blackpool Victoria Hospital	Blackpool	Lancashire
United Kingdom	Royal Bournemouth General Hospital	Bournemouth	Dorset
United Kingdom	St Richard's Hospital	Chichester	West Sussex
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	Russells Hall Hospital	Dudley	West Midlands
United Kingdom	Glasgow Royal Infirmary | Glasgow Clinical Research Facility	Glasgow
United Kingdom	Queen Elizabeth University Hospital	Glasgow	Glasgow City
United Kingdom	University Hospitals Leicester	Leicester	Leicestershire
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Poole Hospital NHS Trust	Poole	Dorset
United Kingdom	Lister Hospital	Stevenage	Hertfordshire
United Kingdom	Great Western Hospital	Swindon
United States	VA Eastern Colorado Health Care System	Aurora	Colorado
United States	Seton Heart Institute	Austin	Texas
United States	Cardiovascular Specialists of Central Maryland, PA	Baltimore	Maryland
United States	John Hopkins Outpatient Center	Baltimore	Maryland
United States	Maryland Cardiovascular Specialists	Baltimore	Maryland
United States	Suburban Hospital	Bethesda	Maryland
United States	National Heart Institute	Beverly Hills	California
United States	Cardiology, PC	Birmingham	Alabama
United States	Cardiovascular & Vein Center of Florida | Bradenton, FL	Bradenton	Florida
United States	Nova Clinical Research | Brandenton, FL	Bradenton	Florida
United States	Advanced Heart Care, LLC | Bridgewater, NJ	Bridgewater	New Jersey
United States	Cardiac Care & Vascular Medicine	Bronx	New York
United States	Kernodle Clinic West, Private Diagnostic Clinic PLLC	Burlington	North Carolina
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Colorado Springs Cardiology	Colorado Springs	Colorado
United States	Harry S. Truman Memorial Veterans Hospital	Columbia	Missouri
United States	IACT Health	Columbus	Georgia
United States	Cardiovascular Associates Research, LLC	Covington	Louisiana
United States	California Heart Specialists	Cypress	California
United States	Southwest Family Medicine Associates	Dallas	Texas
United States	Texas Health Physicians Group - Dallas	Dallas	Texas
United States	Cardiology Associates Research Company	Daytona Beach	Florida
United States	Henry Ford Health System	Detroit	Michigan
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Doylestown Cardiology Associates-VIAA	Doylestown	Pennsylvania
United States	Midwest Cardiovascular Research and Education Foundation	Elkhart	Indiana
United States	IMG Cardiology- Fairfax	Fairfax	Virginia
United States	Eastern Shore Research Institute, LLC | Fairhope, AL	Fairhope	Alabama
United States	Virginia Heart	Falls Church	Virginia
United States	Aa Mrc, Llc	Flint	Michigan
United States	Texas Health Physicians Group - Fort Worth	Fort Worth	Texas
United States	Malcom Randall VA Medical Ctr	Gainesville	Florida
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	The Stern Cardiovascular Foundation, Inc.	Germantown	Tennessee
United States	CHI Health Clinic Heart Institute - Grand Island	Grand Island	Nebraska
United States	Heart Clinic of Hammond	Hammond	Louisiana
United States	Houston Heart & Vascular Associates	Humble	Texas
United States	Apex Cardiology, LLC	Jackson	Tennessee
United States	Baptist Heart -Cardiology - DCT Dept	Jackson	Mississippi
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Western Michigan University School of Medicine	Kalamazoo	Michigan
United States	Logan Health Research	Kalispell	Montana
United States	Clinical Research Consultants	Kansas City	Missouri
United States	St. Luke's Mid America Heart Institute	Kansas City	Missouri
United States	South Texas Cardiovascular Consultants, PLLC / Kerrville, TX	Kerrville	Texas
United States	Kettering Health Network	Kettering	Ohio
United States	Trident Cardiology Associates, PA	Ladson	South Carolina
United States	Carolina Heart Specialists | Lancaster	Lancaster	South Carolina
United States	Virginia Heart	Leesburg	Virginia
United States	Advocate Condell Medical Center	Libertyville	Illinois
United States	CHI Health Nebraska Heart	Lincoln	Nebraska
United States	NJ Heart | Linden, NJ	Linden	New Jersey
United States	Heart Clinic Arkansas	Little Rock	Arkansas
United States	South Denver Cardiology Associates, PC	Littleton	Colorado
United States	William S. Middleton Memorial Veterans Hospital	Madison	Wisconsin
United States	Garden State Heart Care	Manalapan	New Jersey
United States	M Health Fairview	Maplewood	Minnesota
United States	Rama Research LLC | Marion, OH	Marion	Ohio
United States	North Dallas Research Associate | McKinney, TX	McKinney	Texas
United States	Lt. Col. Luke Weathers, Jr. VA Medical Center	Memphis	Tennessee
United States	LifeSpring Research Foundation, LLC	Miami	Florida
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	M Health Fairview Heart Clinic - Fulton	Minneapolis	Minnesota
United States	Mobile Heart Specialists, PC	Mobile	Alabama
United States	PMG Research of Charleston	Mount Pleasant	South Carolina
United States	Edward Hospital-Main Campus	Naperville	Illinois
United States	Southwest Florida Research | Naples, FL	Naples	Florida
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Captain James A. Lovell Federal Health Care Center	North Chicago	Illinois
United States	South Oklahoma Heart Research, LLC	Oklahoma City	Oklahoma
United States	UC Irvine Medical Center	Orange	California
United States	Baptist Health Paducah	Paducah	Kentucky
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	ClinRx Research, LLC	Plano	Texas
United States	Hudson Valley Cardiovascular Practice, PC	Poughkeepsie	New York
United States	Cardiovascular Research of Knoxville	Powell	Tennessee
United States	Monument Health Clinical Research	Rapid City	South Dakota
United States	Reid Physician Associates | Cardiology Department	Richmond	Indiana
United States	Division of Cardiovascular Research at Peconic Bay Med Ctr	Riverhead	New York
United States	Laurelton Heart Specialists	Rosedale	New York
United States	Sutter Heart & Vascular Institute	Sacramento	California
United States	East Coast Institute for Research | St. Augustine, FL	Saint Augustine	Florida
United States	St. Cloud Hospital	Saint Cloud	Minnesota
United States	Salem VA Medical Center	Salem	Virginia
United States	University of Utah Health Care	Salt Lake City	Utah
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	South Texas Cardiovascular Consultants, PLLC	San Antonio	Texas
United States	NorthBay Clinical Research, LLC | Santa Rosa, CA	Santa Rosa	California
United States	Saratoga Clinical Research, LLC	Saratoga Springs	New York
United States	Maine Medical Partners-Maine Health Cardiology	Scarborough	Maine
United States	Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Louisiana Heart Center Research - Slidell	Slidell	Louisiana
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Northwest Houston Heart Center	Tomball	Texas
United States	Harbor - UCLA Medical Center	Torrance	California
United States	Atlanta Heart Specialists, LLC	Tucker	Georgia
United States	University of Arizona Health Science Center	Tucson	Arizona
United States	Northwell Health Phys. Partners Cardiology at Valley Stream	Valley Stream	New York
United States	Blue Coast Research Center, LLC	Vista	California
United States	Kent Hospital	Warwick	Rhode Island
United States	Aspirus Research Institute	Wausau	Wisconsin
United States	Cardiology Partners	Wellington	Florida
United States	Interventional Cardio Medical- DCT Department	West Hills	California
United States	Interventional Cardiology Medical Group | West Hills, CA	West Hills	California
United States	Kansas Nephrology Research Institute, LLC	Wichita	Kansas
United States	Selma Medical Associates	Winchester	Virginia
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina
United States	Mercy Health - St. Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Southern Clinical Research, LLC	Zachary	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  China,  Colombia,  Czechia,  Denmark,  Finland,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of cardiovascular deaths and heart failure events	Composite endpoint. Heart Failure events comprise first and recurrent events	Up to 42 months
Secondary	Time to total (first and recurrent) HF events		Up to 42 months
Secondary	Improvement in NYHA class from Baseline to Month 12		Up to 12 month after start of treatment
Secondary	Change in Total Symptom Score (TSS) from KCCQ.	Patient Reported Outcomes measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)	At baseline, Months 6, 9 and 12
Secondary	Time to first occurrence of composite renal endpoint	Composite renal endpoint: sustained decrease in estimated glomerular filtration rate (eGFR) =50% relative to baseline over at least 4 weeks, or sustained eGFR decline to <15ml/min/1.73m2 or initiation of dialysis or renal transplantation.	Up to 42 months
Secondary	Time to death from any cause		Up to 42 months