A Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure

NCT04157751 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1245-02042019-002946-19
• Study Type: interventional
• Target: 530
• Locations: 15 countries
• Sites: 118

Brief Summary

This is a study in adults who are in hospital for acute heart failure. The purpose of this study is to find out whether starting to take a medicine called empagliflozin soon after first being treated in hospital helps people with acute heart failure. Participants are in the study for about 3 months. At the beginning, participants are still in hospital. Later, they visit the hospital about 3 times and get 1 phone call. Participants are put into 2 groups by chance. One group takes 1 empagliflozin tablet a day. The other group takes 1 placebo tablet a day. Placebo tablets look like empagliflozin tablets but do not contain any medicine. Empagliflozin belongs to a class of medicines known as SGLT-2 inhibitors. It is used to treat type 2 diabetes. During the study, the doctors check whether participants have additional heart failure events like needing to go to the hospital again because of heart failure. The participants answer questions about how their heart failure affects their life. We then compare the results between the empagliflozin and placebo groups. The doctors also regularly check the general health of the participants.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Percentage of Pairwise Comparisons With Wins of Clinical Benefit, a Composite of Death, Number of Heart Failure Events (HFEs), Time to the First HFE and ≥5-point Difference in CfB in KCCQ-TSS After 90 Days of Treatment

  Clinical benefit, a composite of death, number of HFEs, time to first HFE and change from baseline (CfB) in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) after 90 days of treatment. All patients randomised to empagliflozin are compared to all patients randomised to placebo within strata. For any two patients, a patient will win, i.e. achieve a better clinical outcome, as determined by assessing the following criteria sequentially, stopping when an advantage for either patient is shown: 1. Death: death is worse than no death; earlier death is worse; tied if not possible to determine. 2. Number of HFEs: more HFEs is worse; tied, if same number of HFEs. 3. Time to first HFE: earlier HFE is worse; tied, if not possible to determine. 4. KCCQ-TSS CfB at Day 90: more positive CfB is better; the threshold for the difference is \>= 5 for a win; tied, if difference \< 5. The KCCQ-TSS ranges from 0 to 100, where a higher score reflects a better outcome. pct. = percentage

  Up to 90 days. For KCCQ-TSS: at baseline and at day 90.

Secondary Outcomes (10)

• Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment

  At baseline and at day 90.

• Change From Baseline in KCCQ-TSS After 90 Days of Treatment

  At baseline, at day 15, 30 and at day 90.

• Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment

  From baseline to day 30.

• Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge

  Up to 30 days after initial hospital discharge.

• Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation

  Up to 90 days after randomisation.

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Drug: Placebo to Empagliflozin

Interventions

Empagliflozin DRUG

Film-coated tablet

Empagliflozin

Placebo to Empagliflozin DRUG

Film-coated tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Currently hospitalised for the primary diagnosis of acute heart failure (de novo or decompensated chronic HF), regardless of ejection fraction (EF). Patients with a diagnosis of hospitalized heart failure must have HF symptoms at the time of hospital admission
• Evidence of left ventricular ejection fraction (LVEF, either reduced or preserved EF) as per local reading preferably measured during current hospitalisation or in the 12 months prior to randomisation
• Patients must be randomised after at least 24 hours and no later than 5 days after admission, as early as possible after stabilization and while still in hospital
• Patients must fulfil the following stabilisation criteria (while in the hospital):
• SBP ≥100mm Hg and no symptoms of hypotension in the preceding 6 hours,
• no increase in i.v. diuretic dose for 6 hours prior to randomisation,
• no i.v. vasodilators including nitrates within the last 6 hours prior to randomisation
• no i.v. inotropic drugs for 24 hours prior to randomisation.
• Elevated NT-proBNP ≥ 1600pg/mL or BNP ≥400 pg/mL according to the local lab, for patients without atrial fibrillation (AF); or elevated NT-proBNP ≥ 2400pg/mL or BNP ≥600 pg/mL for patients with AF, measured during the current hospitalization or in the 72 hours prior to hospital admission,. For patients treated with an angiotensin receptor neprilysin inhibitor (ARNI) in the previous 4 weeks prior to randomisation, only NT-proBNP values should be used
• HF episode leading to hospitalisation must have been treated with a minimum single dose of 40 mg of i.v. furosemide (or equivalent i.v. loop diuretic defined as 20 mg of torasemide or 1 mg of bumetanide)

You may not qualify if:

• Cardiogenic shock
• Current hospitalisation for acute heart failure primarily triggered by pulmonary embolism, cerebrovascular accident, or acute myocardial infarction (AMI)
• Current hospitalisation for acute heart failure not caused primarily by intravascular volume overload;
• Below interventions in the past 30 days prior to randomisation or planned during the study:
• Major cardiac surgery, or TAVI (Transcatheter Aortic Valve Implantation), or PCI, or Mitraclip
• All other surgeries that are considered major according to investigator judgement
• Implantation of cardiac resynchronisation therapy (CRT) device
• cardiac mechanical support implantation
• Carotid artery disease revascularisation (stent or surgery)
• Acute coronary syndrome / myocardial infarction, stroke or transient ischemic attack (TIA) in the past 90 days prior to randomisation
• Heart transplant recipient, or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement), or planned for palliative care for HF, or currently using left ventricular assist device (LVAD) or intra-aortic balloon pump (IABP) or any other type of mechanical circulatory support, or patients on mechanical ventilation, or patients with planned inotropic support in an outpatient setting
• Haemodynamically significant (severe) uncorrected primary cardiac valvular disease planned for surgery or intervention during the course of the study (note: secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study)
• Impaired renal function, defined as eGFR \< 20 mL/min/1.73 m2 as measured during hospitalization (latest local lab measurement before randomisation) or requiring dialysis
• Type 1 Diabetes Mellitus (T1DM)
• History of ketoacidosis, including diabetic ketoacidosis (DKA)

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (118)

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Irvine

Orange, California, 92865, United States

Location

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Cardiology Associates Research Co.

Daytona Beach, Florida, 32117, United States

Location

University of Florida Health Jacksonville

Jacksonville, Florida, 32209, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Methodist Medical Center

Peoria, Illinois, 61603, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

University Of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cardiovascular Associates of the Delaware Valley

Elmer, New Jersey, 08318, United States

Location

Jefferson Washington Township Hospital

Washington Township, New Jersey, 08080, United States

Location

Erie County Medical Center

Buffalo, New York, 14215, United States

Location

The DeMatteis Center for Cardiac Research and Education

Greenvale, New York, 11548, United States

Location

Stony Brook Medicine

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

North Carolina Heart and Vascular

Raleigh, North Carolina, 27607, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

South Oklahoma Heart Research Group

Oklahoma City, Oklahoma, 73135, United States

Location

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Pharmatex Research

Amarillo, Texas, 79109, United States

Location

Center for Advanced Cardiac Care - Heart Failure Clinic

Plano, Texas, 75093, United States

Location

Inova Fairfax Medical Campus

Falls Church, Virginia, 22042, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Aalst - HOSP Onze-Lieve-Vrouw

Aalst, 9300, Belgium

Location

Brussels - UNIV UZ Brussel

Brussels, 1090, Belgium

Location

AZ Sint-Blasius

Dendermonde, 9200, Belgium

Location

Ziekenhuis Oost-Limburg - Campus Sint-Jan

Genk, 3600, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Liège - HOSP CHR de la Citadelle

Liège, 4000, Belgium

Location

UNIV Ambroise Paré

Mons, 7000, Belgium

Location

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

Location

St. Boniface General Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Beijing Chao-Yang Hospital

Beijing, 100020, China

Location

Beijing AnZhen Hospital

Beijing, 100029, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital

Chengdu, 610041, China

Location

First Affiliated Hospital of Xi'an JiaoTong University

Xi'an, 710061, China

Location

Xiamen Cardiovascular Hospital Xiamen University

Xiamen, 361004, China

Location

University Hospital Brno

Brno, 639 00, Czechia

Location

Univ.Hosp U Svate Anny, I.Internal Clinic-Cardiology,Brno

Brno, 65691, Czechia

Location

University Hospital Motol

Prague, 15006, Czechia

Location

District Hospital, Tabor

Tábor, 390 03, Czechia

Location

Aalborg Universitetsshospital

Aalborg, 9000, Denmark

Location

Frederiksberg Hospital

Frederiksberg, 2000, Denmark

Location

Herlev and Gentofte Hospital

Herlev, 2733, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Viborg Regionhospital

Viborg, 8800, Denmark

Location

Charité - Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

Bremer Institut für Herz- und Kreislaufforschung (BIHKF) am Klinikum Links der Weser

Bremen, 28277, Germany

Location

Herzzentrum Dresden GmbH Universitätsklinik

Dresden, 01307, Germany

Location

Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Giessen, 35392, Germany

Location

Universitätsklinikum Jena

Jena, 07743, Germany

Location

Asklepios Klinik Langen-Seligenstadt GmbH

Langen, 63225, Germany

Location

Klinikum Leverkusen gGmbH, Leverkusen

Leverkusen, 51375, Germany

Location

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, 67063, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, 23538, Germany

Location

Universitätsklinikum Würzburg AÖR

Würzburg, 97080, Germany

Location

Semmelweis University

Budapest, 1088, Hungary

Location

University Debrecen Hospital

Debrecen, 4032, Hungary

Location

University of Pecs

Pécs, 7624, Hungary

Location

Csongrad Country Dr Bugyi Istvan Hosp.

Szentes, 6600, Hungary

Location

Fejer County Saint George University Teaching Hospital

Székesfehérvár, 8000, Hungary

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Università degli Studi "Magna Grecia" - Campus "S. Venuta"

Catanzaro, 88100, Italy

Location

Ospedale della Val di Chiana Santa Margherita

Cortona, 52040, Italy

Location

Az.Osp. Universitaria "Ospedali Riuniti"

Foggia, 71100, Italy

Location

Centro Cardiologico Monzino-IRCCS

Milan, 20138, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Osp. Guglielmo da Saliceto AUSL di Piacenza

Piacenza, 29121, Italy

Location

IRCCS San Raffaele

Roma, 00163, Italy

Location

AO Città della Salute e della

Torino, 10126, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina

Trieste, 34124, Italy

Location

Japan Community Health Care Organization Kyushu Hospital

Fukuoka, Kitakyushu, 806-8501, Japan

Location

Mito Medical Center

Ibaraki, Higashiibaraki-gun, 311-3193, Japan

Location

Kanagawa Cardiovascular and Respiratory Center

Kanagawa, Yokohama, 236-0051, Japan

Location

Shinshu University Hospital

Nagano, Matsumoto, 390-8621, Japan

Location

The Sakakibara Heart Institute of Okayama

Okayama, Okayama, 700-0804, Japan

Location

Osaka University Hospital

Osaka, Suita, 565-0871, Japan

Location

Kawaguchi Cardiovascular and Respiratory Hospital

Saitama, Kawaguchi, 333-0842, Japan

Location

Saitama Sekishikai Hospital

Saitama, Sayama, 350-1305, Japan

Location

Nihon University Itabashi Hospital

Tokyo, Itabashi-ku, 173-8610, Japan

Location

Jeroen Bosch Ziekenhuis-Hertogenbosch

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Gelre Ziekenhuizen Apeldoorn

Apeldoorn, 7334 DZ, Netherlands

Location

TREANT Zorggroep

Emmen, 7824 AA, Netherlands

Location

Groene Hart ziekenhuis

Gouda, 2803 HH, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Sint Jansdal Ziekenhuis

Harderwijk, 3844 DG, Netherlands

Location

Alrijne Leiderdorp

Leiderdorp, 2353 GA, Netherlands

Location

Bravis ziekenhuis, locatie Roosendaal

Roosendaal, 4708 AE, Netherlands

Location

HagaZiekenhuis

The Hague, 2545 AA, Netherlands

Location

Diakonessenhuis Utrecht

Utrecht, 3582 KE, Netherlands

Location

Helse Førde HF, Førde Sentralsjukehus

Førde, N-6812, Norway

Location

Sykehuset Innlandet HF, Avd. Lillehammer

Lillehammer, N-2609, Norway

Location

Akershus Universitetssykehus HF

Lørenskog, N-1478, Norway

Location

Helse Stavanger, Stavanger Universitetssykehus

Stavanger, N-4011, Norway

Location

Universitetssykehuset Nord-Norge, Tromsø

Tromsø, N-9019, Norway

Location

Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia

Gdynia, 81348, Poland

Location

Card.Cli.Mil.Med.Ac.Uni.Cli.Hosp. Cent.Vetera.Hosp.Lodz

Lodz, 90549, Poland

Location

Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard

Lodz, 92-213, Poland

Location

Provincial Specialist M. Kopernik Hospital

Lodz, 93-513, Poland

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, 30120, Spain

Location

Hospital de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Puerta de Hierro

Majadahonda, 28222, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Moises Broggi

Sant Joan Despí, 08970, Spain

Location

Hospital Nuestra Señora de Valme

Seville, 41014, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Sahlgrenska US, Göteborg

Gothenburg, 41345, Sweden

Location

Sahlgrenska Universitetssjukhuset, Östra

Gothenburg, 416 85, Sweden

Location

Related Publications (4)

• Jongs N, Gasparyan SB, Frison L, Schloemer P, Brinker M, Little DJ, Heerspink HJL. Use of eGFR Slope Thresholds as End Point Components in a Kidney Disease Progression Hierarchical Composite End Point. J Am Soc Nephrol. 2025 Dec 1;36(12):2421-2430. doi: 10.1681/ASN.0000000766. Epub 2025 Jun 17.

  PMID: 40526444 DERIVED

• Ferreira JP, Blatchford JP, Teerlink JR, Kosiborod MN, Angermann CE, Biegus J, Collins SP, Tromp J, Nassif ME, Psotka MA, Comin-Colet J, Mentz RJ, Brueckmann M, Nordaby M, Ponikowski P, Voors AA. Mineralocorticoid receptor antagonist use and the effects of empagliflozin on clinical outcomes in patients admitted for acute heart failure: Findings from EMPULSE. Eur J Heart Fail. 2023 Oct;25(10):1797-1805. doi: 10.1002/ejhf.2982. Epub 2023 Aug 22.

  PMID: 37540060 DERIVED

• Kosiborod MN, Angermann CE, Collins SP, Teerlink JR, Ponikowski P, Biegus J, Comin-Colet J, Ferreira JP, Mentz RJ, Nassif ME, Psotka MA, Tromp J, Brueckmann M, Blatchford JP, Salsali A, Voors AA. Effects of Empagliflozin on Symptoms, Physical Limitations, and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial. Circulation. 2022 Jul 26;146(4):279-288. doi: 10.1161/CIRCULATIONAHA.122.059725. Epub 2022 Apr 4.

  PMID: 35377706 DERIVED

• Voors AA, Angermann CE, Teerlink JR, Collins SP, Kosiborod M, Biegus J, Ferreira JP, Nassif ME, Psotka MA, Tromp J, Borleffs CJW, Ma C, Comin-Colet J, Fu M, Janssens SP, Kiss RG, Mentz RJ, Sakata Y, Schirmer H, Schou M, Schulze PC, Spinarova L, Volterrani M, Wranicz JK, Zeymer U, Zieroth S, Brueckmann M, Blatchford JP, Salsali A, Ponikowski P. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022 Mar;28(3):568-574. doi: 10.1038/s41591-021-01659-1. Epub 2022 Feb 28.

  PMID: 35228754 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Boehringer Ingelheim
• Organization: Boehringer Ingelheim, Call Centre

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 8, 2019
• Study Start: May 18, 2020
• Primary Completion: May 28, 2021
• Study Completion: June 2, 2021
• Last Updated: July 19, 2022
• Results First Posted: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

HU (5); JP (9); ES (7); DK (5); US (30); IT (10); DE (11); BE (7); SE (2); CZ (4); PL (4); NO (5); CN (6); NL (10); CA (3)