This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure Symptoms

NCT03448419 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1245-01682017-004073-14
• Study Type: interventional
• Target: 312
• Locations: 11 countries
• Sites: 109

Brief Summary

The primary objective of the study is to evaluate the effect of empagliflozin 10 mg versus placebo on exercise ability using the 6 minute walk test in patients with chronic HF with reduced ejection fraction (LVEF ≤ 40%) Secondary objectives are to assess Patient-Reported Outcome (PRO)

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance

  Change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. If repeated 6MWT measurements were available for the same day, the longest distance was used for analysis. Change from baseline was defined as the distance walked in 6 minutes at week 12 minus the baseline value. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. If a participant was present at the visit at week 12 but did not perform the 6MWT, the participant was evaluated as having walked a distance of 0 meter. If no value was available for week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above.

  At baseline and at week 12

Secondary Outcomes (9)

• Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)

  At baseline and at week 12

• Change From Baseline to Week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized Format (CHQ-SAS) Dyspnea Score

  At baseline and at week 12

• Change From Baseline to Week 6 in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance

  At baseline and at week 6

• Change From Baseline to Week 12 in Clinical Congestion Score

  At baseline and at week 12

• Change From Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms

  At baseline and at week 12

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Empagliflozin DRUG

Film-coated tablet

Also known as: JARDIANCE, JARDIANZ, GIBTULIO

Empagliflozin

Placebo 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:

• Of full age of consent (according to local legislation, usually ≥ 18 years) at screening.
• Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
• Signed and dated written informed consent in accordance with ICHGCP and local legislation prior to admission to the trial
• MWT distance ≤350 m at screening and at baseline.
• Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in NYHA class II-IV
• Chronic HF with reduced EF defined as LVEF ≤ 40 % as per echocardiography at Visit 1 as per local reading (obtained under stable condition).
• Elevated NT-proBNP \> 450 pg/ml for patients without atrial fibrillation (AF) OR NTproBNP \> 600 pg/ml for patients with AF as analysed at the Central laboratory at Visit 1
• Patients must be clinically stable and on appropriate and stable dose of medical therapy for HF (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine), consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at least two weeks prior to Visit 1. The investigator must document the reason in case the patient is not on such medication or if not on target dose of any heart failure medication as per local guidelines.
• Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement).
• Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, and if a device is required, it must have been implanted for at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD.

You may not qualify if:

• Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to Visit 1
• Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 4 weeks prior to Visit 1, and/or during screening period until Visit 2
• Previous or current randomisation in another Empagliflozin Heart Failure trial (i.e. studies 1245.110, 1245.121, 1245-0167)
• Type 1 Diabetes Mellitus (T1DM)
• Impaired renal function, defined as eGFR \< 20 mL/min/1.73 m2 (CKD-EPIcr) or requiring dialysis, as determined at Visit 1
• Symptomatic hypotension or a SBP \< 100 mmHg at Visit 1 or 2
• Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 1 or 2, or SBP \>160mmHg at both Visit 1 and 2
• Atrial fibrillation or atrial flutter with a resting heart rate \>110 bpm documented by ECG at Visit 1 (Screening)
• Unstable angina pectoris in past 30 days prior to Visit 1
• Largest distance walked in 6 minutes (6MWTD) at baseline \<100m.
• Any presence of condition that precludes exercise testing such as:
• claudication,
• uncontrolled (according to investigator judgement) bradyarrhythmia or tachyarrhythmia,
• significant musculoskeletal disease,
• primary pulmonary hypertension,

Sponsors & Collaborators

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

Study Sites (109)

Mobile Heart Specialists, PC

Mobile, Alabama, 36608, United States

Location

The Center for Clinical Trials, Inc.

Saraland, Alabama, 36571, United States

Location

California Heart Specialists

Huntington Beach, California, 92648, United States

Location

Manshadi Heart Institute, Inc

Stockton, California, 95204, United States

Location

University of California Los Angeles

Torrance, California, 90502, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Western Connecticut Health Network

Danbury, Connecticut, 06810, United States

Location

Infinite Clinical Research

Miami, Florida, 33133, United States

Location

Advance Medical Research Center

Miami, Florida, 33135, United States

Location

Bio1 Clinical Research

Miami Beach, Florida, 33140, United States

Location

Pharmacology Research, LLC

North Miami Beach, Florida, 33169, United States

Location

Palm Beach Gardens Research Center, LLC

Palm Beach Gardens, Florida, 33410, United States

Location

East Coast Institute for Research, LLC

Saint Augustine, Florida, 32086, United States

Location

Cozy Research LLC

Zephyrhills, Florida, 33541, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Georgia Arrhythmia Consultants and Research Institute

Warner Robins, Georgia, 31093, United States

Location

St Luke's Clinic - Idaho Cardiology Associates

Boise, Idaho, 83712, United States

Location

Northwest Heart Clinical Research, LLC

Arlington Heights, Illinois, 60005, United States

Location

Clinical Investigation Specialists, Inc

Gurnee, Illinois, 60031, United States

Location

Chicago Medical Research

Hazel Crest, Illinois, 60429, United States

Location

Midwest Heart and Vascular Specialists

Overland Park, Kansas, 66211, United States

Location

Grace Research, LLC

Bossier City, Louisiana, 71111, United States

Location

Grace Research, LLC

Shreveport, Louisiana, 71107, United States

Location

Clinical Trials of America LA, LLC

West Monroe, Louisiana, 71291, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University Of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Med Research One

Florissant, Missouri, 63031, United States

Location

The DOCS

Las Vegas, Nevada, 89113, United States

Location

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

New York Heart Research Foundation, Inc.

Mineola, New York, 11501, United States

Location

PMG Research of Rocky Mount, LLC

Rocky Mount, North Carolina, 27804, United States

Location

PMG Research of Wilmington, LLC

Wilmington, North Carolina, 28401, United States

Location

Rama Research LLC

Marion, Ohio, 43302, United States

Location

Columbia Heart Clinic

Columbia, South Carolina, 29203, United States

Location

Black Hills Cardiovascular Research

Rapid City, South Dakota, 57701, United States

Location

The Jackson Clinic, PA

Jackson, Tennessee, 38301, United States

Location

DiscoveResearch, Inc.

Beaumont, Texas, 77701, United States

Location

Angiocardiac Care of Texas

Houston, Texas, 77025, United States

Location

Mary Washington Hospital Research Department

Fredericksburg, Virginia, 22401, United States

Location

York Clinical Research, LLC

Norfolk, Virginia, 23510, United States

Location

Aspirus Research Institute

Wausau, Wisconsin, 54401, United States

Location

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

University of the Sunshine Coast

Birtinya, Queensland, 4575, Australia

Location

Cairns Base Hospital

Cairns, Queensland, 4870, Australia

Location

Peninsular Health CV Research Unit

Frankston, Victoria, 3199, Australia

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

KMH Cardiology Centres Inc.

Mississauga, Ontario, L5K 2L3, Canada

Location

Toronto Heart Centre

Toronto, Ontario, M4P 1E4, Canada

Location

Sameh Fikry Medicine Professional Corporation

Waterloo, Ontario, N2J 1C4, Canada

Location

CIMS Studienzentrum Bamberg GmbH

Bamberg, 96049, Germany

Location

Klinische Forschung Berlin GbR

Berlin, 10787, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

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

Bremen, 28277, Germany

Location

Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany

Location

Cardiologicum Dresden und Pirna

Dresden, 01277, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt, 60596, Germany

Location

Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

General Hospital of Athens Konstantopoulio-Agia Olga

Athens, 14233, Greece

Location

General Hospital of Athens "G. Gennimatas"

Athens, 15669, Greece

Location

General University Hospital "Attikon"

Haidari, Athens, 12410, Greece

Location

University General Hospital of Heraklion

Herakleion, Crete, 71110, Greece

Location

Univ. Gen. Hosp. of Ioannina

Ioannina, 45500, Greece

Location

University Hospital of Thessaloniki AHEPA

Thessaloniki, 54636, Greece

Location

Centro Cardiologico Monzino-IRCCS

Milan, 20138, Italy

Location

Asst Santi Paolo E Carlo

Milan, 20142, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Università Federico II

Napoli, 80131, Italy

Location

Università degli studi di Palermo

Palermo, 90133, Italy

Location

IRCCS San Raffaele

Roma, 00163, Italy

Location

Sykehuset Østfold Kalnes

Grålum, N-1714, Norway

Location

Vestre Viken, Ringerike Sykehus HF

Hønefoss, N-3511, Norway

Location

Oslo Universitetssykehus HF, Rikshospitalet

Oslo, N-0372, Norway

Location

Helse Stavanger, Stavanger Universitetssykehus

Stavanger, N-4011, Norway

Location

St. Olavs Hospital, Universitetssykehuset i Trondheim

Trondheim, N-7030, Norway

Location

INTERCORE Medical Center

Bydgoszcz, 85-605, Poland

Location

Leszek Bryniarski Specialized Medical Cabinet

Krakow, 30-082, Poland

Location

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

Lodz, 91-425, Poland

Location

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

Lodz, 92-213, Poland

Location

Provincial Specialist M. Kopernik Hospital

Lodz, 93-513, Poland

Location

Independent Public Healthcare, Dept. of Cardiology, Pulawy

Puławy, 24100, Poland

Location

The Provincial Polyclinical Hospital in Torun

Torun, 87-100, Poland

Location

Central Hospital of Medical Academy, Warsaw

Warsaw, 02-097, Poland

Location

4. Military Clinical Hospital with Polyclinic SP ZOZ

Wroclaw, 50 981, Poland

Location

CHLO, EPE - Hospital de Santa Cruz

Carnaxide, 2795, Portugal

Location

CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, 3041-801, Portugal

Location

Centro Hosp. de Leiria-Pombal

Leiria, 2410-197, Portugal

Location

CHLC, EPE - Hospital de Santa Marta

Lisbon, 1169-024, Portugal

Location

CHLO, EPE - Hospital S. Francisco Xavier

Lisbon, 1449-005, Portugal

Location

CHULN, EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

CHTS, EPE - Hospital Padre Américo

Penafiel, 4560-007, Portugal

Location

Centro Hospitalar Universitário São João,EPE

Porto, 4200-319, Portugal

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital San Rafael

Granada, 18001, Spain

Location

Hospital de la Inmaculada Concepción

Granada, 18004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Sahlgrenska US, Göteborg

Gothenburg, 413 45, Sweden

Location

Sahlgrenska Universitetssjukhuset, Östra

Gothenburg, 416 85, Sweden

Location

Akardo Med Site

Stockholm, 11446, Sweden

Location

Related Publications (3)

• Anker SD, Ponikowski P, Wanner C, Pfarr E, Hauske S, Peil B, Salsali A, Ritter I, Koitka-Weber A, Brueckmann M, Lindenfeld J, Abraham WT; EMPERIAL Investigators and National Coordinators. Kidney Function After Initiation and Discontinuation of Empagliflozin in Patients With Heart Failure With and Without Type 2 Diabetes: Insights From the EMPERIAL Trials. Circulation. 2021 Oct 12;144(15):1265-1267. doi: 10.1161/CIRCULATIONAHA.121.054669. Epub 2021 Aug 16. No abstract available.

  PMID: 34397263 DERIVED

• Abraham WT, Ponikowski P, Brueckmann M, Zeller C, Macesic H, Peil B, Brun M, Ustyugova A, Jamal W, Salsali A, Lindenfeld J, Anker SD; EMPERIAL Investigators and National Coordinators. Rationale and design of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic heart failure. Eur J Heart Fail. 2019 Jul;21(7):932-942. doi: 10.1002/ejhf.1486. Epub 2019 Jun 19.

  PMID: 31218819 DERIVED

• Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678.

  PMID: 31081589 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

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

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: February 22, 2018
• First Posted: February 28, 2018
• Study Start: March 20, 2018
• Primary Completion: September 30, 2019
• Study Completion: October 7, 2019
• Last Updated: November 27, 2020
• Results First Posted: October 22, 2020

Record last verified: 2020-11

Locations

DE (14); ES (8); SE (3); AU (5); GR (6); PL (9); US (41); NO (5); CA (4); IT (6); PT (8)