EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved)

Heart Failure Clinical Trial

Official title:

A Phase III Randomised, Double-blind Trial to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg Compared to Placebo, in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03057951
• Other study ID #: 1245.110
• Secondary ID: 2016-002278-11
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2017
• Est. completion date: April 26, 2021

Study information

• Verified date: June 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study in adults with chronic heart failure. People with chronic heart failure may need to be hospitalised for their condition. Some people with chronic heart failure may eventually die from their condition. The purpose of the study is to find out whether a medicine called empagliflozin lowers the chances of patients having to go to hospital for heart failure and whether it improves their survival. The study is open to patients with a type of chronic heart failure called chronic heart failure with preserved ejection fraction.

Participants stay in the study until researchers have enough information about how effective empagliflozin is. It is expected that participants who enter at the very beginning of the enrolment period may be in the study for over 3 years, while participants who enter near the end of the enrolment period may be in the study for less than 2 years. The participants are put into 2 groups. It is decided by chance who gets into which group. One group gets empagliflozin tablets every day and the other group gets placebo tablets every day. Placebo tablets look like empagliflozin tablets but contain no medicine.

Participants visit the doctors regularly. During these visits, the doctors collect information about the participant's health. The doctors want to know how many patients had to go to hospital because of heart failure or who died from cardiovascular disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5988
• Est. completion date: April 26, 2021
• Est. primary completion date: April 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Male or female patient, age >= 18 years at screening. For Japan only: Age >=20 years at screening

• Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association classification) class II-IV and preserved EF (Ejection Fraction)(LVEF (Left Ventricular Ejection Fraction) > 40 %) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide) > 300 pg/ml for patients without AF, OR > 900 pg/ml for patients with AF, analysed at the Central laboratory at Visit 1

• Structural heart disease within 6 months prior to Visit 1, OR documented HHF (Hospitalisation for Heart Failure) within 12 months prior to Visit 1

• Stable dose of oral diuretics, if prescribed

• Signed and dated written ICF (informed consent form)

• Further inclusion criteria apply

Exclusion criteria:

• Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days prior to Visit 1

• Heart transplant recipient or listed for heart transplant

• Acute decompensated HF (Heart Failure)

• Systolic blood pressure (SBP) >= 180 mmHg at Visit 2.

• Symptomatic hypotension and/or a SBP < 100 mmHg

• Indication of liver disease,

• Impaired renal function, defined as eGFR (Estimated Glomerular Filtration Rate) < 20 mL/min/1.73 m2 (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation))cr or requiring dialysis

• History of ketoacidosis

• Current use or prior use of a SGLT (Sodium-glucose co-transporter) -2 inhibitor or combined SGLT-1 and 2 inhibitor

• Currently enrolled in another investigational device or drug trial

• Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial

• Further exclusion criteria may apply

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Empagliflozin
once daily
• Placebo
once daily

Locations

Country	Name	City	State
Argentina	Hospital Interzonal General de Agudos Dr Jose Penna	Bahia Blanca
Argentina	Hospital Italiano Regional del Sur, Bahia Blanca	Bahia Blanca
Argentina	CIPREC	Caba
Argentina	Hospital Italiano de Buenos Aires	Caba
Argentina	Glenny Corp. S.A. Bioclinica Argentina	Ciudad Autonoma Buenos Aires
Argentina	Instituto Cardiovascular de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Centro Médico Viamonte	Ciudad Autonoma de Bs As
Argentina	Sanatorio Güemes	Ciudad Autónoma de Bs As
Argentina	Consultorios Asociados de Endocrinología e Invest Clínica	Ciudad Autonoma de BuenosAires
Argentina	Instituto Medico Elsa Perez SRL (IMEP)	Ciudadela
Argentina	Clinica Privada Colombo- Fundacion Clinica Colombo	Cordoba
Argentina	Instituto Médico DAMIC S.R.L.	Cordoba
Argentina	Centro de Investigaciones Clinicas Instituto del Corazon	Córdoba
Argentina	Hospital Privado	Córdoba
Argentina	Sanatorio Allende S.A.	Córdoba
Argentina	Sanatorio Mayo Privado SA	Córdoba
Argentina	Clinica Coronel Suarez SA	Coronel Suarez
Argentina	Instituto de Cardiología de Corrientes	Corrientes
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	Centro de Investigaciones Médicas	Mar del Plata
Argentina	Hospital Privado de Comunidad	Mar del Plata
Argentina	CER Instituto Médico	Quilmes
Argentina	Instituto de Investigaciones Clínicas de Quilmes	Quilmes
Argentina	Instituto CAICI	Rosario
Argentina	Instituto de Investigaciones Clinicas de Rosario	Rosario
Argentina	Instituto Medico Fundación Grupo Colaborativo Rosario	Rosario
Argentina	Sanatorio Británico	Rosario
Argentina	Sanatorio Plaza	Rosario
Argentina	Centro Cardiovascular Salta	Salta
Argentina	CORDIS S.A., Salta	Salta
Argentina	Corporacion Medica de Gral. San Martin S.A.	San Martin
Argentina	Clinica Mayo	San Miguel de Tucuman
Argentina	Instituto de Cardiología	San Miguel de Tucuman
Argentina	Investigaciones Clinicas Tucuman	San Miguel de Tucumán
Argentina	Centro Medico Luquez	San Vicente
Argentina	Centro de Investigaciones Clínicas del Litoral	Santa Fe
Argentina	Hospital "Dr. José Maria Cullen"	Santa Fé
Argentina	Clínica Olivos	Vicente Lopez
Argentina	CEMEDIC - Centro de Especialidades Medicas	Villa Luro
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Adelaide Medical Research	Ashford	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	The Northern Hospital	Epping	Victoria
Australia	Peninsula Private Hospital	Frankston	Victoria
Australia	Heart and Vascular Research	Fullarton	South Australia
Australia	University Hospital Geelong	Geelong	Victoria
Australia	Pendlebury Research	Kotara	New South Wales
Australia	CORE Research Group	Milton	Queensland
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Mount Hospital	Perth	Western Australia
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Belgium	C.H.U. de Charleroi	Charleroi
Belgium	AZ Sint-Blasius	Dendermonde
Belgium	Ziekenhuis Oost-Limburg - Campus Sint-Jan	Genk
Belgium	AZ Maria Middelares	Gent
Belgium	Grand Hôpital de Charleroi	Gilly
Belgium	Jessa Ziekenhuis - Campus Virga Jesse	Hasselt
Belgium	La Louvière - UNIV CHU Tivoli	La Louvière
Belgium	UZ Leuven	Leuven
Belgium	Liège - HOSP CHR de la Citadelle	Liège
Brazil	FGM - Clínica Paulista de Doenças Cardiovasculares	Bela Vista
Brazil	Hospital Felicio Rocho	Belo Horizonte
Brazil	Hospital Vera Cruz	Belo Horizonte
Brazil	CECAP - Centro de Cardiologia Clínica	Brasília
Brazil	ICDF - Instituto de Cardiologia do Distrito Federal	Brasília
Brazil	L2IP -Instituto de Pesquisas Clínicas Ltda.	Brasília
Brazil	Irmandade da Santa Casa de Misericordia de Curitiba	Campina Grande do Sul
Brazil	CAEP - Centro Avançado de Estudos e Pesquisas Ltda.,Campinas	Campinas
Brazil	Centro Especializado em Cardiol Loema Instituto de Pesq Clin	Campinas
Brazil	IPECC - Instituto de Pesquisa Clínica de Campinas	Campinas
Brazil	Hospital Universitário	Canoas
Brazil	IPCEM - Instituto de Pesquisa Clínica para Estudos Multicêntricos - Universidade de Caxias do Sul	Caxias do Sul
Brazil	Irmandade da Santa Casa de Misericórdia de Curitiba	Curitiba
Brazil	HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás	Goiânia
Brazil	Via Medica	Goiânia
Brazil	ICM - Instituto do Coracao de Marilia	Marília
Brazil	Hospital São Vicente de Paulo	Passo Fundo
Brazil	Centro de Pesquisas em Diabetes	Porto Alegre
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Instituto de Cardiologia Rio Grande do Sul	Porto Alegre
Brazil	Santa Casa de Misericórdia de Porto Alegre	Porto Alegre
Brazil	Hospital Agamenon Magalhaes	Recife
Brazil	H.C.da Fac. de Medicina de Ribeirao Preto	Ribeirao Preto
Brazil	CCBR - Rio de Janeiro - BR	Rio de Janeiro
Brazil	Hospital Universitário Pedro Ernesto UERJ	Rio de Janeiro
Brazil	Cardresearch Cardiologia Assistencial e de Pesquisas Ltda	Santa Efigenia
Brazil	Pesquisare	Santo André
Brazil	Praxis Pesquisa Médica	Santo André
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	São Bernardo do Campo
Brazil	Hospital de Base - Fac Med de Sao Jose do Rio Preto	Sao Jose do Rio Preto
Brazil	Centro de Pesquisa Clinica - CPCLIN	Sao Paulo
Brazil	CEPIC - Centro Paulista de Investigacao Clinica	Sao Paulo
Brazil	INCOR e Hospital das Clínicas da Universidade de São Paulo	Sao Paulo
Brazil	CDEC BRASIL - Centro de Desenvolvimento em Estudos Clínicos Brasil	São Paulo
Brazil	Dr. Consulta	São Paulo
Brazil	CEDOES - Diagnóstico e Pesquisa,Vitória	Vitória
Brazil	Santa Casa de Votuporanga	Votuporanga
Canada	Brampton Cardio Pulmonary Clinic	Brampton	Ontario
Canada	Brampton Research Associates	Brampton	Ontario
Canada	ViaCar Recherche Clinique Inc	Brossard	Quebec
Canada	JBN Medical Diagnostic Services Inc.	Burlington	Ontario
Canada	Cambridge Cardiac Care Inc.	Cambridge	Ontario
Canada	Dr. Saul Vizel	Cambridge	Ontario
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	ViaCar Recherche Clinique Inc	Greenfield Park	Quebec
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Curnew Medicine Professional Corporation	Hamilton	Ontario
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	University Hospital (LHSC)	London	Ontario
Canada	Centre de Dépistage et Recherche Cardiovasculaire Rive-Sud	Longeuil	Quebec
Canada	G.A. Research Associates Ltd	Moncton	New Brunswick
Canada	Clinique Santé Cardio MC	Montreal	Quebec
Canada	McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Montreal General Hospital - McGill University Health Centre	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	PACE (Partners in Advanced Cardiac Evaluation)	Newmarket	Ontario
Canada	Medical Arts Health Research Group	North Vancouver	British Columbia
Canada	M Heffernan Medicine Professional Corp.	Oakville	Ontario
Canada	Kawartha Cardiology Clinical Trials	Peterborough	Ontario
Canada	IUCPQ (Laval University)	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Heart Health Institute	Scarborough	Ontario
Canada	Scarborough Cardiology Research	Scarborough	Ontario
Canada	Cardiovascular Contract Research Organization LTD	Sudbury	Ontario
Canada	Canadian Phase Onward Inc.	Toronto	Ontario
Canada	North York Diagnostic and Cardiac Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Victoria Heart Institute Foundation	Victoria	British Columbia
Canada	Mohan Babapulle Medicine Professional Medicine	Waterloo	Ontario
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Canada	Dr. Louis C.H. Yao	York	Ontario
China	Beijing Friendship Hospital	Beijing
China	Cardiovascular Institute and Fu Wai Hospital	Beijing
China	First Hospital of Jilin University	Changchun
China	2nd Xiangya Hospital of Central South University	Changsha
China	Hunan Provincial People's Hospital	Changsha
China	The Third Hospital of Changsha	Changsha
China	Dongguan People's Hospital	Dongguan
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou
China	Guangzhou First Municipal People's Hospital	Guangzhou
China	The First Afiliated Hospital, Sun Yet-sen University	Guangzhou
China	Haikou People's Hospital	Haikou
China	HaiNan Provincial People's Hospital	Haikou
China	The First Affiliated Hospital of Lanzhou University	Lanzhou
China	The Second Affiliated Hospital of Lanzhou Medical University	Lanzhou
China	The Affiliated Hospital of Southwest Medical University	Luzhou
China	Nanchang University Affiliated 3rd Hospital	Nanchang
China	First Hospital Affiliated with Nanjing Medical University	Nanjing
China	Huashan Hospital, Fudan University	Shanghai
China	General Hospital of Shenyang Military Region	Shenyang
China	Shengjing Hospital of China Medical University	Shenyang
China	Tianjin Union Medical Center Nankai University Affiliated Hospital	Tianjin
China	Renmin Hospital of Wuhan University	Wuhan
China	Tongji Hospital, Tongji University	Wuhan
China	First Affiliated Hospital of Xi'an JiaoTong University	Xi'an
China	Yanbian University Hospital	Yanji
China	the first people hospital of Yue Yang	Yueyang
China	Affiliated Hospital of Jiangsu University	Zhenjiang
Colombia	Centro de Reumatologia y Ortopedia SAS, Barranquilla	Barranquilla
Colombia	Corazon IPS S.A.S.	Barranquilla
Colombia	IPS Centro Cientifico Asistencia	Barranquilla
Colombia	Endocare Research Institute	Bogota
Colombia	CardioColombia S.A.S.	Bogota D.C
Colombia	Centro de Investigaciones Clinicas S.A.S	Cali
Colombia	Fundación Valle del Lili	Cali
Colombia	IPS Centro Medico Julián Coronel S.A.	Cali
Colombia	Centro cardiovascular Aristides	Cartagena
Colombia	Centro de Diagnostico Cardilogico	Cartagena
Colombia	Fundación Cardiovascular de Colombia	Floridablanca
Colombia	Asociacion IPS Medicos Internistas de Caldas	Manizales
Colombia	Promotora Medica Las Americas SA	Medellin
Czechia	Poliklinika Humanitas	Bilovec
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Internal and Cardiology Practice, MUDr. Karel Kamenik, Brno	Brno
Czechia	MUDr. Alexandra Ludkova	Brno
Czechia	Nemocnice Milosrdnych bratri	Brno
Czechia	Univ.Hosp U Svate Anny, I.Internal Clinic-Cardiology,Brno	Brno
Czechia	University Hospital Brno	Brno
Czechia	Vojenska nemocnice Brno	Brno
Czechia	Edumed s.r.o	Broumov
Czechia	MUDr. Jan Hubac, s.r.o. Kardiologicka ambulance	Chrudim
Czechia	Hospital Frydek Mistek	Frydek-Mistek
Czechia	Nemocnice Havlickuv Brod p.o.	Havlickuv Brod
Czechia	Gepamed s.r.o., Pulm. Outpat. Office, Hradec Kralove	Hradec Kralove
Czechia	KardioLouny s.r.o.	Louny
Czechia	InterKardioML s.r.o.	Marianske Lazne
Czechia	Zdenek Vomacka	Olomouc
Czechia	PV-Kardiologie s.r.o.	Pardubice
Czechia	Corintez s.r.o.	Prague
Czechia	Vseobecna fakultni nemocnice V Praze	Praha 2
Czechia	Institute for Clinical and Experimental Medicine	Praha 4
Czechia	University Thomayer's Hospital	Praha 4 - Krc
Czechia	University Hospital Motol	Praha 5
Czechia	Kardio Vaclavik s.r.o.	Prerov
Czechia	Nemocnice Trebic p.o.	Trebic
Czechia	Kardiologicka ambulance	Tremosna
Czechia	Kardiologicka ambulance MUDr. Ferkl s.r.o.	Trutnov
Czechia	Clinical Trials Services s.r.o	Uherske Hradiste
Czechia	Cardiology Private Practice	Unicov
Czechia	Angiocor s.r.o	Zlin
Czechia	KIGE s.r.o	Znojmo
Germany	Universitätsklinikum Aachen, AöR	Aachen
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Praxis Dr. Rieker, Berlin	Berlin
Germany	Vivantes Netzwerk für Gesundheit GmbH	Berlin
Germany	Vivantes Netzwerk für Gesundheit GmbH	Berlin
Germany	Klinikum Bielefeld gGmbH	Bielefeld
Germany	Augusta-Kranken-Anstalt gGmbH	Bochum
Germany	Praxis Dr. Menzel	Dessau-Roßlau
Germany	St. Johannes Hospital Dortmund	Dortmund
Germany	Städtisches Klinikum Dresden	Dresden
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Studienzentrum Bocholderstraße	Essen
Germany	ClinPhenomics GmbH & Co KG, Frankfurt	Frankfurt
Germany	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Asklepios Klinik Langen-Seligenstadt GmbH	Langen
Germany	Märkische Gesundheitsholding GmbH & Co. KG, Klinikum Lüdenscheid	Lüdenscheid
Germany	Praxis Dr. Sarnighausen, Lüneburg	Lüneburg
Germany	Katholisches Klinikum Mainz	Mainz
Germany	Gemeinschaftspraxis Drs. Kohler/Salbach, Mannheim	Mannheim
Germany	Deutsches Herzzentrum München	München
Germany	Gemeinschaftspraxis Dres Haggenmiller/Jeserich	Nürnberg
Germany	Kardiologische Praxis Papenburg	Papenburg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Praxis Dr. Stenzel, Riesa	Riesa
Germany	Zentrum für Klinische Forschung	Wangen im Allgäu
Germany	Josephs-Hospital Warendorf	Warendorf
Germany	Kardiologische Praxis, Wermsdorf	Wermsdorf
Germany	Petrus-Krankenhaus	Wuppertal
Hungary	Lausmed Kft. Outpatient Unit of Internal Medicine	Baja
Hungary	Belgyogyaszati es Kardiologiai Maganrendelo	Bekescsaba
Hungary	Bajcsy-Zsilinszky Hospital and Clinic	Budapest
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Clinexpert Kft.	Budapest
Hungary	Milit.Hosp.-State Health Cent.	Budapest
Hungary	Semmelweis University	Budapest
Hungary	Uzsoki Street Hospital, Budapest	Budapest
Hungary	Nehezlegzes Ambulancia	Debrecen
Hungary	University Debrecen Hospital	Debrecen
Hungary	Bugat Pal Hospital, Gyongyos	Gyongyos
Hungary	Studium Egeszseghaz Kft.	Kalocsa
Hungary	Selye Janos Hospital Komarom	Komarom
Hungary	Dorottya Kanizsai Hospital	Nagykanizsa
Hungary	Medifarma-98 Kft.	Nyiregyhaza
Hungary	Dr. Nagy Laszlo Kardiologiai Maganrendeles	Oroshaza
Hungary	Da Vinci Private Clinic	Pecs
Hungary	University of Pecs	Pecs
Hungary	Fejer County Saint George University Teaching Hospital	Szekesfehervar
Hungary	Veszpremi Sziv es Egeszseg Centrum	Veszprem
India	Doctor Jivraj Mehta Smarak Health Foundation	Ahmedabad
India	Kamalnayan Bajaj Hospital	Aurangabad
India	Narayana Institute of Cardiac Sciences	Bangalore
India	Rajarajeswari Medical College	Bengaluru
India	Apollo Speciality Hospital	Chennai
India	Madras Medical Mission,	Chennai
India	Medanta-The Medicity	Gurgaon
India	GNRC Hospital	Guwahati
India	B.M. Birla Heart research Centre	Kolkatta
India	Siddhi Hospital	Nashik
India	Vijan Cardiac and Critical Care Centre	Nasik
India	Batra Hospital and Medical Research Centre	New Delhi
India	Fortis Escorts Heart Institute	New Delhi
India	GB Pant Hospital	New Delhi
India	Sir Gangaram Hospital	New Delhi
Italy	Azienda Ospedaliera G. Rummo	Benevento
Italy	ASST Papa Giovanni XXIII - A.O. Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliera Universitaria Arcispedale Sant'Anna	Cona (FE)
Italy	Ospedale della Val di Chiana Santa Margherita	Cortona
Italy	Centro Cardiologico Monzino-IRCCS	Milano
Italy	Milano Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	AOU Policlinico Umberto I	Roma
Italy	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma
Italy	Istituto Clinico Humanitas	Rozzano (MI)
Italy	IRCCS Gruppo Multimedica	Sesto San Giovanni (MI)
Italy	Azienda Servizi Sanitari 1 Triestina	Trieste
Japan	Kasugai Municipal Hospital	Aichi, Kasugai
Japan	Japanese Red Cross Nagoya Daini Hospital	Aichi, Nagoya
Japan	Chiba Heart Clinic	Chiba, Chiba
Japan	Kimitsu Chuo Hospital	Chiba, Kisarazu
Japan	Seikeikai New Tokyo Heart Clinic	Chiba, Matsudo
Japan	Ehime Prefectural Central Hospital	Ehime, Matsuyama
Japan	Matsuyama Shimin Hospital	Ehime, Matsuyama
Japan	Uwajima City Hospital	Ehime, Uwajima
Japan	Fukuiken Saiseikai Hospital	Fukui, Fukui
Japan	Fukuoka University Chikushi Hospital	Fukuoka, Chikushino
Japan	Fukuokaken Saiseikai Futsukaichi Hospital	Fukuoka, Chikushino
Japan	Kyushu University Hospital	Fukuoka, Fukuoka
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka, Fukuoka
Japan	Saiseikai Fukuoka General Hospital	Fukuoka, Fukuoka
Japan	Japan Community Health Care Organization Kyushu Hospital	Fukuoka, Kitakyushu
Japan	Steel Memorial Yawata Hospital	Fukuoka, Kitakyushu
Japan	Shirakawa Kosei General Hospital	Fukushima, Shirakawa
Japan	Ogaki Municipal Hospital	Gifu, Ogaki
Japan	Chuno Kosei Hospital	Gifu, Seki
Japan	Fukuyama City Hospital	Hiroshima, Fukuyama
Japan	Shobara Red Cross Hospital	Hiroshima, Shobara
Japan	Matsuda Cardiovascular Clinic	Hokkaido, Sapporo
Japan	Teine Keijinkai Clinic	Hokkaido, Sapporo
Japan	Tomakomai City Hospital	Hokkaido, Tomakomai
Japan	Otaru Kyokai Hospital	Hokkaido,Otaru
Japan	Hyogo Prefectural Amagasaki General Medical Center	Hyogo, Amagasaki
Japan	Hyogo Brain and Heart Center	Hyogo, Himeji
Japan	National Hospital Organization Kobe Medical Center	Hyogo, Kobe
Japan	Mito Medical Center	Ibaraki, Higashiibaraki-gun
Japan	Tokushukai Koga General Hospital	Ibaraki, Koga
Japan	National Hospital Organization Kanazawa Medical Center	Ishikawa, Kanazawa
Japan	Mitoyo General Hospital	Kagawa, Kanonji
Japan	Kagawa Prefectural Central Hospital	Kagawa, Takamatsu
Japan	Sekishinkai Second Kawasaki Saiwai Clinic	Kanagawa, Kawasaki
Japan	Yamamoto Clinic	Kanagawa, Sagamihara
Japan	Kanagawa Cardiovascular and Respiratory Center	Kanagawa, Yokohama
Japan	Japanese Red Cross Kumamoto Hospital	Kumamoto, Kumamoto
Japan	Seiwakai Suizenji Touya Hospital	Kumamoto, Kumamoto
Japan	Kumamoto Rosai Hospital	Kumamoto, Yatsushiro
Japan	Omi Medical Center	Kusatsu
Japan	Uji-Tokushukai Medical Center	Kyoto, Uji
Japan	National Hospital Organization Sendai Medical Center	Miyagi, Sendai
Japan	Sendai Kousei Hospital	Miyagi, Sendai
Japan	Sendai Tokushukai Hospital	Miyagi, Sendai
Japan	Miyazaki Medical Association Hospital	Miyazaki, Miyazaki
Japan	Hokushin General Hospital	Nagano, Nakano
Japan	Nagasaki Medical Center	Nagasaki, Omura
Japan	Oita Medical Center	Oita, Oita
Japan	Okayama City General Medical Center	Okayama, Okayama
Japan	Naha City Hospital	Okinawa, Naha
Japan	Nanbu Tokushukai Hospital	Okinawa, Shimajiri-gun
Japan	Urasoe General Hospital	Okinawa, Urasoe
Japan	Higashiosaka City Medical Center	Osaka, Higashiosaka
Japan	Kitano Hospital	Osaka, Osaka
Japan	Yodogawa Christian Hospital	Osaka, Osaka
Japan	Hokusetsu General Hospital	Osaka, Takatsuki
Japan	Kosekai Iwatsuki-minami Hospital	Saitama, Saitama
Japan	San-Ai Hospital	Saitama, Saitama
Japan	Tokushima Prefectural Central Hospital	Tokushima, Tokushima
Japan	National Hospital Organization Tokyo Medical Center	Tokyo, Meguro-ku
Japan	Ome Municipal General Hospital	Tokyo, Ome
Japan	Tokyo Rosai Hospital	Tokyo, Ota-ku
Japan	Sekino Hospital	Tokyo, Toshima-ku
Japan	Minami Wakayama Medical Center	Wakayama, Tanabe
Japan	Kanmon Medical Center	Yamaguchi, Shimonoseki
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-Do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Wonju Severance Christian Hosp	Wonju-si
Mexico	Hospital Cardiologica Aguascalientes	Aguascalientes
Mexico	Centro de Investigacion Biomedica y Farmaceutica, S.C.	Distrito Federal
Mexico	Cardiologia Clinica e Intervencionista	Guadalajara
Mexico	Diseño y Planeación en Investigación Médica SC	Guadalajara
Mexico	Hospital Ramon Garibay	Guadalajara
Mexico	Unidad de Investigacion Clinica Cardiometabolica de Occident	Guadalajara
Mexico	Centro de Investigación Clinica Acelerada, S.C.	Mexico
Mexico	CEDOPEC-Ctro Esp en Diab, Obesidad y Prev de Enf Cardiovasc	México
Mexico	Instituto Cardiovascular de Monclova, S de RL de CV	Monclova
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Nuevo Leon
Mexico	Centro Integral Medico SJR S.C.	San Juan del Rio
Mexico	Cardioarritmias e Investigación S.C	San Luis Potosi
Mexico	Centro de Investigacion Cardiovascular y Metabolica	Tijuana
Mexico	Centro de Investigacion Medica Alberto Bazzoni S.A. de C.V.	Torreon
Netherlands	Ziekenhuisgroep Twente locatie Almelo	Almelo
Netherlands	Amsterdam UMC Locatie VUMC	Amsterdam
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Netherlands	BovenIJ Ziekenhuis	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis, Locatie West	Amsterdam
Netherlands	Rode Kruis Ziekenhuis Beverwijk	Beverwijk
Netherlands	Tergooiziekenhuizen locatie Blaricum	Blaricum
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Ziekenhuis Gelderse Vallei	EDE
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Maastricht University	Maastricht
Netherlands	Diaconessenhuis Meppel	Meppel
Netherlands	St. Antonius ziekenhuis, locatie Nieuwegein	Nieuwegein
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Netherlands	Franciscus Gasthuis	Rotterdam
Netherlands	De Heel - Zaans Medisch Centrum	Zaandam
Netherlands	Gelre Ziekenhuis Zutphen	Zutphen
Poland	ClinicMed Badurski i wspolnicy Spolka Jawna, Bialystok	Bialystok
Poland	KLIMED Marek Klimkiewicz	Bialystok
Poland	Univ. Clinic Hosp, Bialystok	Bialystok
Poland	American Heart of Poland Sp. z o.o.	Bielsko-Biala
Poland	NZOZ Centrum Medyczne KERmed	Bydgoszcz
Poland	Polsko-Amerykanskie Kliniki Serca	Chorzow
Poland	American Heart of Poland Sp. z o.o.	Dabrowa Gornicza
Poland	Poradnia Kardiologiczna Jaroslaw Jurowiecki	Gdansk
Poland	University Clinical Center, Gdansk	Gdansk
Poland	Indywidualna Specjalistyczna Praktyka Lekarska	Gdynia
Poland	NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog.	Gdynia
Poland	Szpital Zakonu Bonifratow Sp. z o.o.	Katowice
Poland	Specialistic Cardiology&Hypertension Out-patient Clin,Kielce	Kielce
Poland	Krakow Specialistic Hospital of John Paul II	Krakow
Poland	Leszek Bryniarski Specialized Medical Cabinet	Krakow
Poland	ETG Lodz	Lodz
Poland	Individual Specialized Practice	Lodz
Poland	Nzoz Salus	Lodz
Poland	Lowickie Cardiology Center	Lowicz
Poland	American Heart of Poland Sp. z o.o.	Nysa
Poland	Medicome Sp. z o.o.	Oswiecim
Poland	NZOZ HEUREKA, Piaseczno	Piaseczno
Poland	Specialized Practice Dr. Janusz Spyra	Ruda Slaska
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	Lukmed Lukasz Wozniak	Siedlce
Poland	ETG Skierniewice	Skierniewice
Poland	KO-MED Centra Kliniczne Staszow	Staszow
Poland	The Provincial Polyclinical Hospital in Torun	Torun
Poland	American Heart of Poland Sp. z o.o.	Tychy
Poland	American Heart of Poland Sp. z o.o.	Ustron
Poland	ETG Warszawa	Warszawa
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny	Warszawa
Poland	4. Military Clinical Hospital with Polyclinic SP ZOZ	Wroclaw
Poland	Zgierskie Center of Cardiology MED-PRO	Zgierz
Poland	Specialist Hospital J. Dietla NZOZ Specialized Clinic "Gemini"	Zychlin
Romania	Spitalul Clinic De Urgenta "Prof. Dr. Agrippa Ionescu"	Balotesti
Romania	C.M.D.T.A. NEOMED, Brasov	Brasov
Romania	CMDTA Washington, Bucharest	Bucharest
Romania	Emergency Clinical Hospital 'Sf. Panteliomon'	Bucharest
Romania	Emergency University Hospital, Bucharest	Bucharest
Romania	Emergency University Hospital, Bucharest	Bucharest
Romania	Prof.C.C.Iliescu Hospital, National Institute of Cardiology	Bucharest
Romania	Clinica Medicala Data Plus SRL	Bucuresti
Romania	Spitalul Clinic "Prof. Dr. Theodor Burghele"	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Romania	S.C Cardiomed S.R.L	Craiova
Romania	Spital Judetean Deva	Deva
Romania	S.C Medicali's S.R.L	Timisoara
Romania	Spitalul Clinic Judetean de Urgenta, Timisoara	Timisoara
Singapore	Khoo Teck Puat Hospital	Singapore
Singapore	National Heart Center	Singapore
Singapore	National University Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
South Africa	Cardiology Clinical Research	Alberton
South Africa	Iatros International	Bloemfontein
South Africa	Universitas Hospital Cardiology Research	Bloemfontein
South Africa	Corbod Research	Cape Town
South Africa	Tiervlei Trial Centre	Cape Town
South Africa	TREAD Research	Cape Town
South Africa	Excellentis Clinical Trials	George
South Africa	Chris Hani Baragwanath Hospital: Cardiology Department	Johannesburg
South Africa	Clinresco	Johannesburg
South Africa	MERC Research	Kempton Park
South Africa	Into Research	Pretoria
South Africa	Dr JM Engelbrecht	Somerset West
South Africa	Clinical Projects Research	Worcester
Spain	Hospital Quiron. I.C.U.	Barcelona
Spain	Hospital Sanitas CIMA	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Clínico de Santiago	Santiago de Compostela
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
United Kingdom	Barnet General Hospital	Barnet
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Park & St Francis Surgery	Eastleigh
United Kingdom	Wycombe General Hospital	High Wycombe
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	St Mary's Hospital	Newport
United Kingdom	Morriston Hospital	Swansea
United States	Capital Cardiology Associates, PC	Albany	New York
United States	Alpena General Hospital	Alpena	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Northwest Heart Clinical Research, LLC	Arlington Heights	Illinois
United States	Asheville Cardiology Associates	Asheville	North Carolina
United States	Grady Clinical Research Center	Atlanta	Georgia
United States	Seton Heart Institute	Austin	Texas
United States	Maryland Cardiovascular Specialists	Baltimore	Maryland
United States	MedStar Health Research Institute	Baltimore	Maryland
United States	Metropolitan Cardiovascular Consultants	Beltsville	Maryland
United States	Deaconess Billings Clinic Research Center	Billings	Montana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Integrated Heart Care	Boca Raton	Florida
United States	Grace Research, LLC	Bossier City	Louisiana
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Health Clinical Research	Bozeman	Montana
United States	Advanced Heart Care, LLC	Bridgewater	New Jersey
United States	Cardiac Care and Vascular Medicine, PLLC	Bronx	New York
United States	CHEAR Center LLC	Bronx	New York
United States	Kernodle Clinic West	Burlington	North Carolina
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Lowcountry Center for Veterans Research	Charleston	South Carolina
United States	Novant Health Heart and Vascular Institute	Charlotte	North Carolina
United States	Trinity Medical WNY, PC	Cheektowaga	New York
United States	Cardiac Health Management Network, P.C.	Chester	Virginia
United States	Mount Sinai Hospital	Chicago	Illinois
United States	Southeast Clinical Research, LLC	Chiefland	Florida
United States	Morton Plant Mease Health Care	Clearwater	Florida
United States	VA Northeast Ohio Healthcare System	Cleveland	Ohio
United States	Palmetto Health	Columbia	South Carolina
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Soltero Cardiovascular Research Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Cardiology Consultants of Danville, Inc	Danville	Virginia
United States	Accel Research Sites	DeLand	Florida
United States	Iowa Heart Center	Des Moines	Iowa
United States	Doylestown Health Cardiology	Doylestown	Pennsylvania
United States	Midwest Cardiovascular Research and Education Foundation	Elkhart	Indiana
United States	Alpine Research Organization	Farmington	Utah
United States	Integrative Research Associates	Fort Lauderdale	Florida
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	University of California San Francisco	Fresno	California
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	The Stern Cardiovascular Center	Germantown	Tennessee
United States	Nebraska Heart Institute	Grand Island	Nebraska
United States	East Mountain Medical Associates, PC	Great Barrington	Massachusetts
United States	Cardiology Associates of Bellin Health	Green Bay	Wisconsin
United States	Angiocardiac Care of Texas	Houston	Texas
United States	Biopharma Informatic, Inc. Research Center	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
United States	Heart Center Research, LLC	Huntsville	Alabama
United States	St. Francis Medical Group-Indiana Heart Physicians, Inc	Indianapolis	Indiana
United States	Nature Coast Clinical Research	Inverness	Florida
United States	Apex Cardiology/ Research Associates of Jackson	Jackson	Tennessee
United States	Jackson Heart Clinic, P.A.	Jackson	Mississippi
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Lycoming Internal Medicine, Inc	Jersey Shore	Pennsylvania
United States	Richard M Kastelic and Associates	Johnstown	Pennsylvania
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Private Practice Leadership, LLC	Katy	Texas
United States	La Mesa Cardiac Center	La Mesa	California
United States	Purushotham, Akther & Roshan Kotha, MD Inc.	La Mesa	California
United States	Healthcare Partners LLC	Las Vegas	Nevada
United States	Palm Research Center	Las Vegas	Nevada
United States	Cardiovascular Group PC	Lawrenceville	Georgia
United States	Clinical Trials of America, Inc	Lenoir	North Carolina
United States	Maine Research Associates	Lewiston	Maine
United States	South Denver Cardiology Associates, PC	Littleton	Colorado
United States	Long Beach Center for Clinical Research	Long Beach	California
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	Norton Heart Specialists	Louisville	Kentucky
United States	Meriter Wisconsin Heart	Madison	Wisconsin
United States	Garden State Heart Care, PC	Manalapan	New Jersey
United States	Carient Heart and Vascular	Manassas	Virginia
United States	North Shore University Hospital	Manhasset	New York
United States	Rama Research LLC	Marion	Ohio
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Methodist University Hospital	Memphis	Tennessee
United States	Merced Vein and Vascular Center	Merced	California
United States	Cardiovascular Research Center of South Florida	Miami	Florida
United States	Elite Clinical Research	Miami	Florida
United States	Clinical Trials of America, LLC	Monroe	Louisiana
United States	Advocate Health and Hospitals Corporation	Naperville	Illinois
United States	Long Island Cardiovascular Consultants	New Hyde Park	New York
United States	LSU Health Sciences Center	New Orleans	Louisiana
United States	Harlem Cardiology	New York	New York
United States	Mount Sinai - PRIME	New York	New York
United States	Captain James A. Lovell Federal Health Care Center	North Chicago	Illinois
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	South Oklahoma Heart Research Group	Oklahoma City	Oklahoma
United States	University of California Irvine	Orange	California
United States	Orlando Health Inc.	Orlando	Florida
United States	Peninsula Research, Inc.	Ormond Beach	Florida
United States	Research Integrity, LLC	Owensboro	Kentucky
United States	MD Medical Research	Oxon Hill	Maryland
United States	CHI Health Midlands	Papillion	Nebraska
United States	McLaren Northern Michigan Hospital	Petoskey	Michigan
United States	Baylor Scott and White Health	Plano	Texas
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	Medical College of Virginia Hospitals	Richmond	Virginia
United States	Reid Hospital	Richmond	Indiana
United States	Covigilant Research, LLC	Riverside	California
United States	Roanoke Heart Institute PLC	Roanoke	Virginia
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	Rockford Cardiovascular Associates	Rockford	Illinois
United States	Laurelton Heart Specialist, PC	Rosedale	New York
United States	Clearwater Cardiovascular Consultants	Safety Harbor	Florida
United States	Saint Louis University	Saint Louis	Missouri
United States	St. Louis Center for Clinical Research	Saint Louis	Missouri
United States	St. Louis Heart and Vascular, P.C.	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Salem VA Medical Center	Salem	Virginia
United States	University of California San Francisco	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Saratoga Clinical Research, LLC	Saratoga Springs	New York
United States	Meridian Clinical Research, LLC	Savannah	Georgia
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Sanford Research	Sioux Falls	South Dakota
United States	Beacon Medical Group Clinical Research	South Bend	Indiana
United States	Northwell Health	Southampton	New York
United States	Palmetto Research Center, LLC	Spartanburg	South Carolina
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Advent Health Medical Group	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	University of California	Torrance	California
United States	Atlanta Heart Specialists, LLC	Tucker	Georgia
United States	Orange County Research Center	Tustin	California
United States	Blue Coast Cardiology	Vista	California
United States	Aspirus Research Institute	Wausau	Wisconsin
United States	York Hospital, WellSpan Health	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Colombia,  Czechia,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Romania,  Singapore,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF)	Failure with preserved Ejection Fraction (HFpEF). The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 * number of patients with event / time at risk [years].; Time at risk [years] = Sum of time at risk [days] over all patients in a treatment group / 365.25.; Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.	From randomization until completion of the planned treatment phase, up to 1403 days.
Secondary	Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent)	Reported is the total number of adjudicated HHF events (first and recurrent) which occurred.	From randomization until completion of the planned treatment phase, up to 1403 days.
Secondary	eGFR (CKD-EPI) cr Slope of Change From Baseline	Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR(CKD-EPI)cr) slope of change from baseline.; Available on-treatment change-from-baseline data were used. The slope represents the long term effect of eGFR change from baseline and provides the yearly rate of decline.; Timepoints after baseline were included in calculation of slope of change from baseline.; The slope per patient was calculated using a random coefficient model with terms for treatment, region, baseline status of diabetes, age, sex, left ventricular ejection fraction (LVEF) and glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula (eGFR (CKD-EPI)cr) at baseline and in addition the factors "time", "treatment-by-time interaction", and "baseline eGFR (CKD-EPI)cr-by-time interaction".	At baseline, week 4, 12, 32, 52, 76, 100, 124, 148, 172 and week 196, up to 1043 days.
Secondary	Time to the First Event in the Composite Renal Endpoint: Chronic Dialysis, Renal Transplant, or Sustained Reduction in eGFR (CKD-EPI)cr	Chronic dialysis was defined as dialysis with a frequency of twice per week or more for at least 90 days.; Sustained was determined by two or more consecutive post-baseline central laboratory measurement separated by at least 30 days.; Reduction in glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) was defined as reduction in eGFR from baseline =40%, eGFR <15 mL/min/1.73 m^2 for patients with baseline eGFR =30 mL/min/1.73 m^2, or eGFR <10 mL/min/1.73 m^2 for patients with baseline eGFR <30 mL/min/1.73 m^2.; The incidence rate per 100 patient years (100 * number of patients with event / time at risk [years]) is reported. Time at risk [year] is calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25.; Abbreviation: Patient-years (pt-yrs).	From randomization until completion of the planned treatment phase, up to 1403 days.
Secondary	Time to First Adjudicated Hospitalisation for Heart Failure (HHF)	Time to first adjudicated HHF. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 * number of patients with event / time at risk [years].; Time at risk [years] = Sum of time at risk [days] over all patients in a treatment group / 365.25.; Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.	From randomization until completion of the planned treatment phase, up to 1403 days.
Secondary	Time to Adjudicated Cardiovascular (CV) Death	Time to adjudicated CV death. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 * number of patients with event / time at risk [years].; Time at risk [years] = Sum of time at risk [days] over all patients in a treatment group / 365.25.; Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.	From randomization until completion of the planned treatment phase, up to 1403 days.
Secondary	Time to All-cause Mortality	Time to all-cause mortality. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 * number of patients with event / time at risk [years].; Time at risk [years] = Sum of time at risk [days] over all patients in a treatment group / 365.25.; Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.	From randomization until completion of the planned treatment phase, up to 1403 days.
Secondary	Time to Onset of Diabetes Mellitus (DM) in Patients With Pre-DM	Time to onset of DM (defined as HbA1c =6.5% or as diagnosed by the investigator) in patients with pre-DM.; Pre-DM was defined as no history of DM and no HbA1c =6.5% before treatment, and a pre-treatment HbA1c value of =5.7% and <6.5%.; The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 * number of patients with event / time at risk [years].; Time at risk [years] = Sum of time at risk [days] over all patients in a treatment group / 365.25.; Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.	From randomization until completion of the planned treatment phase, to 1403 days.
Secondary	Change From Baseline in Kansas City Cardiomyopathy Questionaire (KCCQ) Clinical Summary Score at Week 52	The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in patients with Heart Failure. The KCCQ-clinical summary score comprises the following domains: Symptom frequency, symptom burden and physical limitation. The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status.; For patients who died, a worst score (score of 0) was imputed for the score at all subsequent scheduled visits after the date of death where the score would have been assessed.; Change from baseline in KCCQ-score at week 52 was modeled using a MMRM with visit (week 12, 32 and 52) as repeated measures, adjusted mean (standard error) at week 52 is reported.	At baseline and at week 12, week 32 and week 52.
Secondary	Occurrence of All-cause Hospitalisation (First and Recurrent)	Occurrence of all-cause hospitalisation (first and recurrent). Total number of all cause hospitalisations is reported.	From randomization until completion of the planned treatment phase, up to 1403 days.

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