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

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 Reduced Ejection Fraction (HFrEF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03057977
• Other study ID #: 1245.121
• Secondary ID: 2016-002280-34
• Status: Completed
• Phase: Phase 3
• Start date: March 6, 2017
• Est. completion date: May 28, 2020

Study information

• Verified date: April 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3730
• Est. completion date: May 28, 2020
• Est. primary completion date: May 1, 2020
• 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 reduced EF (Ejection Fraction) (LVEF (Left Ventricular Ejection Fraction) <=40%) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide)

• If EF >= 36% to <= 40%: NT-proBNP >= 2500 pg/ml or patients without AF (atrial fibrillation/atrial flutter) and NT-proBNP >= 5000 pg/ml for patients with AF

• If EF >= 31% to <= 35%: NT-proBNP >= 1000 pg/ml for patients without AF and NT-proBNP >=2000 pg/ml for patients with AF

• If EF<= 30%: NT-proBNP >= 600 pg/ml for patients without AF and NT-proBNP >=1200 pg/ml for patients with AF

• EF = 40% and hospitalization for heart failure in the past 12 months: NTproBNP = 600 pg/ml for patients without AF and NT-proBNP >= 1200 pg/ml for patients with AF

• Appropriate dose of medical therapy for HF consistent with prevailing local and international CV (Cardiovascular) guidelines, stable for at least 1 week prior to Visit 1

• Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines

• 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

• 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)) 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 study

• 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 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	CCBR - Buenos Aires - AR	Ciudad Autonoma Buenos Aires
Argentina	Consultorios Asociados de Endocrinología e Invest Clínica	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	Instituto Medico Elsa Perez SRL (IMEP)	Ciudadela
Argentina	Clínica 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	Clínica Olivos	Olivos
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 Parque	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	CCBR Tucuman	San Miguel de Tucumán
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	Instituto de Cardiología	Tucumán
Argentina	CEMEDIC - Centro de Especialidades Medicas	Villa Luro
Australia	SA-Heart Ashford Specialist Centre	Ashford	South Australia
Australia	The Northern Hospital	Epping	Victoria
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Heart and Vascular Research	Fullarton	South Australia
Australia	University Hospital Geelong	Geelong	Victoria
Australia	CORE Research Group	Milton	Queensland
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Mater Hospital Brisbane	South Brisbane	Queensland
Belgium	AZ Sint-Jan Brugge	Brugge
Belgium	C.H.U. de Charleroi	Charleroi
Belgium	AZ Sint-Blasius	Dendermonde
Belgium	Ziekenhuis Oost-Limburg - Campus Sint-Jan	Genk
Belgium	AZ Sint-Lucas - Campus Sint Lucas	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	AZ Sint-Maarten	Mechelen
Brazil	Cardresearch Cardiologia Assistencial e de Pesquisas Ltda	Belo Horizonte
Brazil	Hospital Felicio Rocho	Belo Horizonte
Brazil	Hospital Vera Cruz	Belo Horizonte
Brazil	CCBR - Brasília	Brasília
Brazil	CECAP - Centro de Cardiologia Clínica	Brasília
Brazil	ICDF - Instituto de Cardiologia do Distrito Federal	Brasília
Brazil	Hospital Angelina Caron	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	Hospital de Messejana Dr. Carlos Alberto Studart Gomes	Fortaleza
Brazil	Barroso e Sebba Ltda	Goiania
Brazil	HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás	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	Ribeirão Preto
Brazil	CCBR - Rio de Janeiro - BR	Rio de Janeiro
Brazil	Hospital Universitário Pedro Ernesto UERJ	Rio De Janeiro - RJ
Brazil	Pesquisare	Santo André
Brazil	Praxis Pesquisa Médica	Santo André
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	São Bernardo do Campo
Brazil	Fundacao Faculdade Regional de Medicina, Sao Jose	Sao Jose do Rio Preto
Brazil	Centro de Pesquisa Clinica - CPCLIN	Sao Paulo
Brazil	CEPIC - Centro Paulista de Investigacao Clinica	Sao Paulo
Brazil	FGM - Clínica Paulista de Doenças Cardiovasculares	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	JBN Medical Diagnostic Services Inc.	Burlington	Ontario
Canada	Cambridge Cardiac Care Inc.	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	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	Southlake Regional Health Centre	Newmarket	Ontario
Canada	M Heffernan Medicine Professional Corp.	Oakville	Ontario
Canada	Kawartha Cardiology Clinical Trials	Peterborough	Ontario
Canada	IUCPQ (Laval University)	Quebec
Canada	Centre de sante et de services sociaux de Beauce	Saint George-de-Beauce	Quebec
Canada	Heart Health Institute	Scarborough	Ontario
Canada	Scarborough Cardiology Research	Scarborough	Ontario
Canada	Health Sciences North	Sudbury	Ontario
Canada	Canadian Phase Onward Inc.	Toronto	Ontario
Canada	Diabetes Heart Research Centre	Toronto	Ontario
Canada	North York Diagnostic and Cardiac Centre	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
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
Czechia	Poliklinika Humanitas	Bilovec
Czechia	Medicus Services Ltd.	Brandys Nad
Czechia	Internal and Cardiology Practice, MUDr. Karel Kamenik, Brno	Brno
Czechia	MUDr. Alexandra Ludkova	Brno
Czechia	Nemocnice Milosrdnych bratri	Brno
Czechia	Vojenska nemocnice Brno	Brno
Czechia	Edumed s.r.o	Broumov
Czechia	MUDr. Jan Hubac, s.r.o. Kardiologicka ambulance	Chrudim
Czechia	Nemocnice ve Frydku-Mistku, prispevkova organizace	Frydek-Mistek
Czechia	MUDr. Ladislav Busak	Louny
Czechia	Zdenek Vomacka	Olomouc
Czechia	PV-Kardiologie s.r.o.	Pardubice
Czechia	University Hospital Motol	Prag 5
Czechia	General Faculty Hospital, Prague	Prague 2
Czechia	Thomayer Hospital	Praha 4 - Krc
Czechia	Kardio Vaclavik s.r.o.	Prerov
Czechia	Clinic of Cardiology, Pribram	Pribram
Czechia	Hospital Trebic, p.o.	Trebic
Czechia	Masaryk Hospital, Usti nad Labem	Usti nad Labem
Czechia	Angiocor s.r.o	Zlin
Czechia	KIGE s.r.o	Znojmo
France	HOP de Bayonne	Bayonne
France	HOP Jean Minjoz	Besançon
France	HOP Louis Pradel	Bron
France	HOP Côte de Nacre	Caen
France	HOP Arnaud de Villeneuve	Montpellier
France	HOP La Pitié Salpêtrière	Paris
France	Centre Hospitalier de Pau	Pau
France	HOP Haut-Lévêque	Pessac
France	HOP Rangueil	Toulouse
France	INS Louis Mathieu	Vandoeuvre-lès-Nancy
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	Klinikum Bielefeld gGmbH	Bielefeld
Germany	Praxis Dr. Menzel	Dessau-Roßlau
Germany	St. Johannes Hospital Dortmund	Dortmund
Germany	GWT-TUD GmbH	Dresden
Germany	Städtisches Klinikum 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	Asklepios Klinik St. Georg	Hamburg
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 St. Hildegardiskrankenhaus, Mainz	Mainz
Germany	Deutsches Herzzentrum München	München
Germany	Kardiologische Gemeinschaftspraxis Nienburg	Nienburg
Germany	Kardiologische Praxis Papenburg	Papenburg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Praxis Dr. Stenzel, Riesa	Riesa
Germany	Zentrum für Klinische Forschung	Wangen
Germany	Josephs-Hospital Warendorf	Warendorf
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	Clinexpert Kft.	Budapest
Hungary	Gottsegen Gyorgy Hungarian Instit.of Cardiology,Budapest	Budapest
Hungary	Milit.Hosp.-State Health Cent.	Budapest
Hungary	Semmelweis University	Budapest
Hungary	Uzsoki Street Hospital, Budapest	Budapest
Hungary	Nehezlegzes Ambulancia	Debrecen
Hungary	Bugat Pal Hospital, Gyongyos	Gyongyos
Hungary	Selye Janos Hospital Komarom	Komarom
Hungary	Dorottya Kanizsai Hospital	Nagykanizsa
Hungary	Dr. Nagy Laszlo Kardiologiai Maganrendeles	Oroshaza
Hungary	Da Vinci Maganklinika	Pecs
Hungary	Pecsi Tudomanyegyetem	Pécs
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	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 (AR)
Italy	Centro Cardiologico Monzino-IRCCS	Milano
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma
Italy	Umberto I Pol. di Roma-Università di Roma La Sapienza	Roma
Italy	Azienda Servizi Sanitari 1 Triestina	Trieste
Japan	Kasugai Municipal Hospital	Aichi, Kasugai
Japan	Japanese Red Cross Nagoya Daini Hospital	Aichi, Nagoya
Japan	Nagoya Kyoritsu Hospital	Aichi, Nagoya
Japan	Toyota Memorial Hospital	Aichi, Toyota
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	Aso Co.,Ltd Iizuka Hospital	Fukuoka, Iizuka
Japan	Japan Community Health Care Organization Kyushu Hospital	Fukuoka, Kitakyushu
Japan	Steel Memorial Yawata Hospital	Fukuoka, Kitakyushu
Japan	Ogaki Municipal Hospital	Gifu, Ogaki
Japan	Chuno Kosei Hospital	Gifu, Seki
Japan	Fukuyama City Hospital	Hiroshima, Fukuyama
Japan	JA Hiroshima General Hospital	Hiroshima, Hatsukaichi
Japan	Shobara Red Cross Hospital	Hiroshima, Shobara
Japan	National Hospital Organization Hakodate Hospital	Hokkaido, Hakodate
Japan	Teine Keijinkai Clinic	Hokkaido, Sapporo
Japan	Tomakomai City Hospital	Hokkaido, Tomakomai
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	National Hospital Organization Kanazawa Medical Center	Ishikawa, Kanazawa
Japan	Mitoyo General Hospital	Kagawa, Kanonji
Japan	Kagawa Prefectural Central Hospital	Kagawa, Takamatsu
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	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	The Cardiovascular Center of Sendai	Miyagi, Sendai
Japan	Miyazaki Medical Association Hospital	Miyazaki, Miyazaki
Japan	Hokushin General Hospital	Nagano, Nakano
Japan	Nagasaki Medical Center	Nagasaki, Omura
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	Seichokai Bell Land General Hospital	Osaka, Sakai
Japan	Hokusetsu General Hospital	Osaka, Takatsuki
Japan	Kosekai Iwatsuki-minami Hospital	Saitama, Saitama
Japan	San-Ai Hospital	Saitama, Saitama
Japan	Kusatsu General Hospital	Shiga, Kusatsu
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
Korea, Republic of	Chungnam National University Hospital	Daejeon
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	Seoul National University Bundang Hospital	Sungnam
Korea, Republic of	Wonju Severance Christian Hosp	Wonju
Mexico	Hospital Cardiologica Aguascalientes	Aguascalientes
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Ciudad de Mexico
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	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
Mexico	Hospital Dr Angel Leano	Zapopan
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	HMC Bronovo	Den Haag
Netherlands	Ziekenhuis Gelderse Vallei	EDE
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Vasculair Onderzoek Centrum	Hoorn
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht
Netherlands	Diaconessenhuis Meppel	Meppel
Netherlands	St. Antonius ziekenhuis, locatie Nieuwegein	Nieuwegein
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Netherlands	Ziekenhuis Bernhoven Uden	Uden
Netherlands	Vie Curi Medisch Centrum	Venlo
Netherlands	De Heel - Zaans Medisch Centrum	Zaandam
Netherlands	Gelre Ziekenhuis Zutphen	Zutphen
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	Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia	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	Individual Specialized Practice	Lodz
Poland	Nzoz Salus	Lodz
Poland	SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia	Lodz
Poland	Lowickie Cardiology Center	Lowicz
Poland	American Heart of Poland Sp. z o.o.	Nysa
Poland	Medicome Sp. z o.o.	Oswiecim
Poland	Specialized Practice Dr. Janusz Spyra	Ruda Slaska
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	Lukmed Lukasz Wozniak	Siedlce
Poland	Clinmedica Research Omc sp. z o.o. sp.k., 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	Central Hospital of Medical Academy, Warsaw	Warsaw
Poland	McM Polimedica	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
Spain	Hospital Quiron. I.C.U.	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar
Spain	Hospital de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Complejo Hospitalario Universitario de Orense	Orense
Spain	Hospital Clínico de Santiago	Santiago de Compostela
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
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	Luton and Dunstable University Hospital	Luton
United Kingdom	St Mary's Hospital	Newport
United Kingdom	Morriston Hospital	Swansea
United States	Cambridge Medical Trials	Alexandria	Louisiana
United States	Alpena General Hospital	Alpena	Michigan
United States	AnMed Health Clinical Research	Anderson	South Carolina
United States	Anne Arundel Medical Center	Annapolis	Maryland
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	Augusta University	Augusta	Georgia
United States	Johns Hopkins University Hospital School of Medicine	Baltimore	Maryland
United States	MedStar Health Research Institute	Baltimore	Maryland
United States	Metropolitan Cardiovascular Consultants	Beltsville	Maryland
United States	Integrated Heart Care	Boca Raton	Florida
United States	Tufts Medical Center	Boston	Massachusetts
United States	Advanced Heart Care, LLC	Bridgewater	New Jersey
United States	Cardiac Care and Vascular Medicine, PLLC	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	Ralph H. Johnson VA Medical Center	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	University of Chicago	Chicago	Illinois
United States	Morton Plant Mease Health Care	Clearwater	Florida
United States	Palmetto Health	Columbia	South Carolina
United States	William Jennings Bryan Dorn VA Medical Center	Columbia	South Carolina
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Louisiana Heart Center	Covington	Louisiana
United States	Nature Coast Clinical Research	Crystal River	Florida
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	Avail Clinical Research, LLC	DeLand	Florida
United States	Doylestown Health Cardiology	Doylestown	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Midwest Cardiovascular Research and Education Foundation	Elkhart	Indiana
United States	Alpine Research Organization	Farmington	Utah
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Integrative Research Associates	Fort Lauderdale	Florida
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	East Mountain Medical Associates, PC	Great Barrington	Massachusetts
United States	Northwell Health	Great Neck	New York
United States	The Methodist Hospital	Houston	Texas
United States	St. Francis Medical Group-Indiana Heart Physicians, Inc	Indianapolis	Indiana
United States	Nature Coast Clinical Research	Inverness	Florida
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	La Mesa Cardiac Center	La Mesa	California
United States	Mount Sinai School of Medicine	Lake Success	New York
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	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	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	Clinical Trials of America, LLC	Monroe	Louisiana
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Harlem Cardiology	New York	New York
United States	St. Luke's Roosevelt Hospital	New York	New York
United States	Captain James A. Lovell Federal Health Care Center	North Chicago	Illinois
United States	South Oklahoma Heart Research Group	Oklahoma City	Oklahoma
United States	University of California Irvine	Orange	California
United States	Peninsula Research, Inc.	Ormond Beach	Florida
United States	Research Integrity, LLC	Owensboro	Kentucky
United States	Cardiology Consultants, Inc	Pensacola	Florida
United States	The Heart Hospital	Plano	Texas
United States	Hunter Holmes McGuire VA Medical Center	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	Saint Louis University	Saint Louis	Missouri
United States	SLHV	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Salem VA Medical Center	Salem	Virginia
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Meridian Clinical Research, LLC	Savannah	Georgia
United States	Beacon Medical Group Clinical Research	South Bend	Indiana
United States	Palmetto Research Center, LLC	Spartanburg	South Carolina
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	University of Toledo	Toledo	Ohio
United States	University of California	Torrance	California
United States	Spectrum Clinical Research	Towson	Maryland
United States	Orange County Research Center	Tustin	California
United States	Blue Coast Cardiology	Vista	California
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,  Czechia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF)	Time to the first event of adjudicated cardiovascular (CV) death or adjudicated hospitalisation for heart failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.; Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.	From randomisation until completion of the planned treatment period, up to 1040 days.
Secondary	Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent)	Reported is the total number of HHF events (first and recurrent) which occurred.; All data up to the end of the planned treatment period (including the data after the end of treatment for patients not completing the treatment period as planned) from all randomised patients was used.	From randomisation until completion of the planned treatment phase, up to 1040 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) [mL/min/1.73m2] slope of change from baseline.; Available on-treatment change-from-baseline data were to be used. Patients without on-treatment data after randomisation were not to be included in this analysis. Slope represents the long term effect on eGFR.; Timepoints after baseline were included in calculation of slope of change from baseline. Descriptive statistic (mean(standard error)) is reported.	Assessed at baseline, week 4, 12, 32, 52, 76, 100, 124, 148 and at end of treatment (EOT), up to 1040 days.
Secondary	Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr	Time to the first event in the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), renal transplant, or sustained reduction in Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr).; The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.; Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.	From randomisation until completion of the planned treatment period, up to 1040 days.
Secondary	Time to First Adjudicated Hospitalisation for Heart Failure (HHF)	Time to first adjudicated Hospitalisation for Heart Failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.; Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.	From randomisation until completion of the planned treatment period, up to 1040 days.
Secondary	Time to Adjudicated Cardiovascular (CV) Death	Time to adjudicated CV (Cardiovascular) death. The incidence rate (patients with events per 100 person years at risk) is reported.; The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.; Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.	From randomisation until completion of the planned treatment period, up to 1040 days.
Secondary	Time to All-cause Mortality	Time to all-cause mortality. The incidence rate (patients with events per 100 person years at risk) is reported.; The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.; Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.	From randomisation until completion of the planned treatment period, up to 1040 days.
Secondary	Time to Onset of Diabetes Mellitus (DM)	Time to onset of DM (Glycated haemoglobin (HbA1c) =6.5% or as diagnosed by the investigator) in patients with pre-DM (no history of DM and no HbA1c =6.5% before treatment, and a pre-treatment HbA1c value of 5.7 to <6.5%). The incidence rate (patients with events per 100 person years at risk) is reported.; The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.; Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.	From randomisation until completion of the planned treatment period, up to 1040 days.
Secondary	Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52	Change from baseline in KCCQ (Kansas City cardiomyopathy questionnaire) 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, selfefficacy, 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) is imputed at all subsequent scheduled visits after the date of death.; Standard error is adjusted standard error. 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.	Assessed at baseline, week 12, week 32 and week 52.
Secondary	Number of All-cause Hospitalizations (First and Recurrent)	Number of all-cause hospitalizations (first and recurrent).	From randomisation until completion of the planned treatment phase, up to 1040 days.

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