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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Empagliflozin
Placebo
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Of full age of consent (according to local legislation, usually ≥ 18 years) at screening.
  • Male or female patients. Women of child bearing potential (WOCBP) 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
  • Six minute walk test (6MWT) distance ≤350 m at screening and at baseline.
  • Patients with CHF diagnosed for at least 3 months before Visit 1, and currently in NYHA class II-IV
  • Chronic heart failure (CHF) with preserved Ejection fraction (EF) defined as left ventricle ejection fraction(LVEF) > 40 % as per echocardiography at Visit 1 per local reading and no prior measurement of LVEF ≤ 40% under stable conditions.
  • Elevated N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) > 300 pg/ml for patients without atrial fibrillation (AF), OR > 600 pg/ml for patients with AF, as analysed at the Central laboratory at Visit 1

  • Patients must have at least one of the following evidence of heart failure (HF):

    • Structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) documented by echocardiogram at Visit 1, OR
    • Documented Hospitalization for Heart Failure (HHF) within 12 months prior to Visit 1
  • Consistent with prevailing CV guidelines, if oral diuretics are prescribed to control symptoms, patients must be on an appropriate and stable dose of oral diuretics for at least 2 weeks prior to Visit 1 to control symptoms.
  • Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement).

Exclusion Criteria:

  • 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 transient ischemic attack in past 90 days prior to Visit 1
  • Acute decompensated HF (exacerbation of CHF) 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, 1245-0168)
  • 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 systolic blood pressure (SBP) < 100 mmHg at Visit 1 or 2
  • 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,
    • severe obesity (body mass index ≥40.0 kg/m2),
    • orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries)
    • amputation with artificial limb without stable prosthesis function for the past 3 months
    • Any condition that in the opinion of the investigator would contraindicate the assessment of 6MWT
  • Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial.
  • ICD implantation within 1 month prior to Visit 1 or planned during the course of the trial
  • Implanted cardiac resynchronisation therapy (CRT)
  • Treatment with i.v. iron therapy or erythropoietin (EPO) within 3 months prior to screening.
  • Further exclusion criteria applies

Sites / Locations

  • Mobile Heart Specialists, PC
  • The Center for Clinical Trials, Inc.
  • California Heart Specialists
  • Manshadi Heart Institute, Inc
  • University of California Los Angeles
  • University of Colorado Denver
  • Western Connecticut Health Network
  • Bio1 Clinical Research
  • Infinite Clinical Research
  • Advance Medical Research Center
  • Pharmacology Research, LLC
  • Palm Beach Gardens Research Center, LLC
  • East Coast Institute for Research, LLC
  • Cozy Research LLC
  • Grady Memorial Hospital
  • Georgia Arrhythmia Consultants and Research Institute
  • St Luke's Clinic - Idaho Cardiology Associates
  • Northwest Heart Clinical Research, LLC
  • Clinical Investigation Specialists, Inc
  • Chicago Medical Research
  • Midwest Heart and Vascular Specialists
  • Grace Research, LLC
  • Grace Research, LLC
  • Clinical Trials of America LA, LLC
  • Beth Israel Deaconess Medical Center
  • John D. Dingell VA Medical Center
  • Med Research One
  • Cox Medical Center South
  • The DOCS
  • Rutgers Robert Wood Johnson Medical School
  • Albany Stratton VA Medical Center Albany, NY
  • UNC REX Healthcare
  • PMG Research of Rocky Mount, LLC
  • PMG Research of Wilmington, LLC
  • Rama Research LLC
  • Columbia Heart Clinic
  • Black Hills Cardiovascular Research
  • The Jackson Clinic, PA
  • DiscoveResearch, Inc.
  • Angiocardiac Care of Texas
  • Acacia Medical Research Institute,LLC
  • Mary Washington Hospital Research Department
  • York Clinical Research, LLC
  • Canberra Hospital
  • University of the Sunshine Coast
  • Peninsular Health CV Research Unit
  • University of Calgary
  • KMH Cardiology Centres Inc.
  • Toronto Heart Centre
  • Sameh Fikry Medicine Professional Corporation
  • CIMS Studienzentrum Bamberg GmbH
  • Klinische Forschung Berlin GbR
  • Charité - Universitätsmedizin Berlin
  • Cardiologicum Dresden und Pirna
  • Universitätsklinikum Düsseldorf
  • IKF Pneumologie GmbH & Co. KG
  • Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH
  • Universitätsklinikum Köln (AöR)
  • Universitätsklinikum Leipzig
  • Universitätsklinikum Magdeburg AöR
  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Universitätsklinikum Ulm
  • Universitätsklinikum Würzburg
  • General Hospital of Athens Konstantopoulio-Agia Olga
  • General Hospital of Athens "G. Gennimatas"
  • General Hospital of Chalkida
  • University General Hospital of Heraklion
  • Univ. Gen. Hosp. of Ioannina
  • University Hospital of Thessaloniki AHEPA
  • Centro Cardiologico Monzino-IRCCS
  • Asst Santi Paolo E Carlo
  • ASST Grande Ospedale Metropolitano Niguarda
  • Ospedale Regina Montis Regalis
  • Università Federico II
  • Università degli studi di Palermo
  • IRCCS San Raffaele
  • Sykehuset Østfold Kalnes
  • Oslo Universitetssykehus HF, Rikshospitalet
  • Helse Stavanger, Stavanger Universitetssykehus
  • St. Olavs Hospital, Universitetssykehuset i Trondheim
  • INTERCORE Medical Center
  • 10.Military Clin.Hospital&Polyclinic
  • Leszek Bryniarski Specialized Medical Cabinet
  • Card.Cli.Mil.Med.Ac.Uni.Cli.Hosp. Cent.Vetera.Hosp.Lodz
  • Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard
  • Provincial Specialist M. Kopernik Hospital
  • Independent Public Healthcare, Dept. of Cardiology, Pulawy
  • Central Hospital of Medical Academy, Warsaw
  • 4. Military Clinical Hospital with Polyclinic SP ZOZ
  • CHLO, EPE - Hospital de Santa Cruz
  • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
  • Centro Hosp. de Leiria-Pombal
  • CHLC, EPE - Hospital de Santa Marta
  • CHLO, EPE - Hospital S. Francisco Xavier
  • CHULN, EPE - Hospital de Santa Maria
  • Centro Hospitalar Universitário São João,EPE
  • Hospital General Universitario de Alicante
  • Hospital Germans Trias i Pujol
  • Hospital San Rafael
  • Hospital de la Inmaculada Concepción
  • Hospital Universitario Virgen de las Nieves
  • Hospital La Princesa
  • Hospital Ramón y Cajal
  • Hospital Clínico de Valencia
  • Sahlgrenska US, Göteborg
  • Sahlgrenska Universitetssjukhuset, Östra
  • Skånes universitetssjukhus, Lund
  • Akardo Med Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Empagliflozin

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline to Week 12 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes in Standardised Conditions (6MWTD)
Change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions (6MWTD). If repeated 6-minutes walk test (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.

Secondary Outcome Measures

Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)
Change from baseline in KCCQ-TSS was defined as the endpoint value at week 12 minus the last available measurement before start of treatment with randomised study medication. The KCCQ is 23 item self-administered questionnaire and comprises 7 domains: physical limitation, symptom frequency, symptom burden, symptom stability, social limitation, self-efficacy and quality of life. Additionally 3 summary scores exist: TSS, clinical summary score, and overall summary score. The scores of the KCCQ domains and summary scores range from 0 to 100, with higher score indicating better outcome. If no questionnaire was available at 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. If no questionnaire was available at baseline, change from baseline was not imputed.
Change From Baseline to Week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized Format (CHQ-SAS) Dyspnea Score
Change from baseline in CHQ-SAS was defined as the endpoint value at week 12 minus the last available endpoint value before start of treatment with randomised study medication. The CHQ-SAS evaluates 3 domains: dyspnoea, fatigue, and emotional function. Scores of the domains range from 1 to 7, with higher score indicating better quality of life. If no questionnaire was available at 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. If no questionnaire was available at baseline, change from baseline was not imputed.
Change From Baseline to Week 6 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes
Change from baseline to week 6 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. Change from baseline was defined as the distance walked in 6 minutes at Week 6 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 6 but did not perform the 6-Minuted Walking Test, the participant was evaluated as having walked a distance of 0 meter. If no value was available for Week 6, an imputed value was used.
Change From Baseline in Clinical Congestion Score at Week 12
Change from baseline to week 12 in Clinical Congestion score is defined as the score-value at week 12 minus the score-value at baseline. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. The Clinical Congestion Score (summary score) is based on 3 items: orthopnoea, jugular venous distention (JVD) and oedema. Each item was assessed through a 4-measure questionnaire, which was further converted to a standardised 4-point scale ranging from 0 to 3, with 0 indicating no or fewer symptoms and 3 indicating continous or more symptoms. If at least 2 of the 3 items are not missing, the summary score is calculated as: (average over items JVD, orthopnea and oedema actually answered)*3. The summary score ranges from 0 to 9, with lower value indicating better health, and higher value indicating worse health. Mean is adjusted mean.
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms at Week 12
Change from baseline to week 12 in PGI-S of Heart Failure Symptoms. The Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of symptoms severity, specifically: shortness of breath, fatigue and swelling. The PGI-S asks the Patient to choose one response that best describes how his/her heart failure symptoms, specifically: shortness of breath, fatigue and swelling are now on a 5-category scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Dyspnea Severity at Week 12
Change from baseline to week 12 in Patient Global Impression of Severity (PGI-S) of dyspnoea. The PGI-S of Dyspnoea is a 1-item questionnaire designed to assess the participant´s impression of symptom severity, specifically dyspnoea. The PGI-S item asks the participant to choose one response that best describes how his/her dyspnoea is now on a 5-category scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.
Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12
The Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of change in heart failure symptoms, specifically: shortness of breath, fatigue, and swelling. The PGI-C asks the patient to choose one Response that best describes the overall change (if any) in his/her heart failure symptoms, specifically: shortness of breath, fatigue, and swelling since he/she started taking the study medication on a 7- category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).
Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12
The PGI-C in Dyspnoea is a 1-item questionnaire designed to assess the patient's Impression of change in dyspnoea. The PGI-C asks the patient to choose one response that best describes the change (if any) in his/her shortness of breath when performing usual activities since he/she started taking the study medication on a 7-category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).
Relative Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NTproBNP) at Week 12
Relative change from baseline to week 12 in N-terminal pro-brain natriuretic peptide (NTproBNP). Relative change from baseline is expressed as ratio of week 12 to baseline. Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication. Mean is adjusted mean.

Full Information

First Posted
February 22, 2018
Last Updated
November 12, 2020
Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT03448406
Brief Title
This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure Symptoms.
Official Title
A Phase III Randomised, Double-blind Trial to Evaluate the Effect of 12 Weeks Treatment of Once Daily EMPagliflozin 10 mg Compared With Placebo on ExeRcise Ability and Heart Failure Symptoms, In Patients With Chronic HeArt FaiLure With Preserved Ejection Fraction (HFpEF) (EMPERIAL - Preserved)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
March 20, 2018 (Actual)
Primary Completion Date
October 4, 2019 (Actual)
Study Completion Date
October 9, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 (6MWT) in patients with chronic heart failure (CHF) with preserved ejection fraction (LVEF > 40%). Secondary objectives are to assess Patient-Reported Outcome (PRO)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
315 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Other Intervention Name(s)
JARDIANCE, JARDIANZ, GIBTULIO
Intervention Description
Film-coated tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Film-coated tablet
Primary Outcome Measure Information:
Title
Change From Baseline to Week 12 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes in Standardised Conditions (6MWTD)
Description
Change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions (6MWTD). If repeated 6-minutes walk test (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.
Time Frame
At baseline and at Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)
Description
Change from baseline in KCCQ-TSS was defined as the endpoint value at week 12 minus the last available measurement before start of treatment with randomised study medication. The KCCQ is 23 item self-administered questionnaire and comprises 7 domains: physical limitation, symptom frequency, symptom burden, symptom stability, social limitation, self-efficacy and quality of life. Additionally 3 summary scores exist: TSS, clinical summary score, and overall summary score. The scores of the KCCQ domains and summary scores range from 0 to 100, with higher score indicating better outcome. If no questionnaire was available at 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. If no questionnaire was available at baseline, change from baseline was not imputed.
Time Frame
At baseline and at Week 12
Title
Change From Baseline to Week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized Format (CHQ-SAS) Dyspnea Score
Description
Change from baseline in CHQ-SAS was defined as the endpoint value at week 12 minus the last available endpoint value before start of treatment with randomised study medication. The CHQ-SAS evaluates 3 domains: dyspnoea, fatigue, and emotional function. Scores of the domains range from 1 to 7, with higher score indicating better quality of life. If no questionnaire was available at 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. If no questionnaire was available at baseline, change from baseline was not imputed.
Time Frame
At baseline and at Week 12
Title
Change From Baseline to Week 6 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes
Description
Change from baseline to week 6 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. Change from baseline was defined as the distance walked in 6 minutes at Week 6 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 6 but did not perform the 6-Minuted Walking Test, the participant was evaluated as having walked a distance of 0 meter. If no value was available for Week 6, an imputed value was used.
Time Frame
At baseline and at Week 6
Title
Change From Baseline in Clinical Congestion Score at Week 12
Description
Change from baseline to week 12 in Clinical Congestion score is defined as the score-value at week 12 minus the score-value at baseline. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. The Clinical Congestion Score (summary score) is based on 3 items: orthopnoea, jugular venous distention (JVD) and oedema. Each item was assessed through a 4-measure questionnaire, which was further converted to a standardised 4-point scale ranging from 0 to 3, with 0 indicating no or fewer symptoms and 3 indicating continous or more symptoms. If at least 2 of the 3 items are not missing, the summary score is calculated as: (average over items JVD, orthopnea and oedema actually answered)*3. The summary score ranges from 0 to 9, with lower value indicating better health, and higher value indicating worse health. Mean is adjusted mean.
Time Frame
At baseline and at Week 12
Title
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms at Week 12
Description
Change from baseline to week 12 in PGI-S of Heart Failure Symptoms. The Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of symptoms severity, specifically: shortness of breath, fatigue and swelling. The PGI-S asks the Patient to choose one response that best describes how his/her heart failure symptoms, specifically: shortness of breath, fatigue and swelling are now on a 5-category scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.
Time Frame
At baseline and at Week 12
Title
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Dyspnea Severity at Week 12
Description
Change from baseline to week 12 in Patient Global Impression of Severity (PGI-S) of dyspnoea. The PGI-S of Dyspnoea is a 1-item questionnaire designed to assess the participant´s impression of symptom severity, specifically dyspnoea. The PGI-S item asks the participant to choose one response that best describes how his/her dyspnoea is now on a 5-category scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.
Time Frame
At baseline and at Week 12
Title
Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12
Description
The Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of change in heart failure symptoms, specifically: shortness of breath, fatigue, and swelling. The PGI-C asks the patient to choose one Response that best describes the overall change (if any) in his/her heart failure symptoms, specifically: shortness of breath, fatigue, and swelling since he/she started taking the study medication on a 7- category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).
Time Frame
Week 12
Title
Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12
Description
The PGI-C in Dyspnoea is a 1-item questionnaire designed to assess the patient's Impression of change in dyspnoea. The PGI-C asks the patient to choose one response that best describes the change (if any) in his/her shortness of breath when performing usual activities since he/she started taking the study medication on a 7-category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).
Time Frame
Week 12
Title
Relative Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NTproBNP) at Week 12
Description
Relative change from baseline to week 12 in N-terminal pro-brain natriuretic peptide (NTproBNP). Relative change from baseline is expressed as ratio of week 12 to baseline. Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication. Mean is adjusted mean.
Time Frame
Within 3 weeks prior to treatment start and at Week 12.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Of full age of consent (according to local legislation, usually ≥ 18 years) at screening. Male or female patients. Women of child bearing potential (WOCBP) 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 Six minute walk test (6MWT) distance ≤350 m at screening and at baseline. Patients with CHF diagnosed for at least 3 months before Visit 1, and currently in NYHA class II-IV Chronic heart failure (CHF) with preserved Ejection fraction (EF) defined as left ventricle ejection fraction(LVEF) > 40 % as per echocardiography at Visit 1 per local reading and no prior measurement of LVEF ≤ 40% under stable conditions. Elevated N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) > 300 pg/ml for patients without atrial fibrillation (AF), OR > 600 pg/ml for patients with AF, as analysed at the Central laboratory at Visit 1 Patients must have at least one of the following evidence of heart failure (HF): Structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) documented by echocardiogram at Visit 1, OR Documented Hospitalization for Heart Failure (HHF) within 12 months prior to Visit 1 Consistent with prevailing CV guidelines, if oral diuretics are prescribed to control symptoms, patients must be on an appropriate and stable dose of oral diuretics for at least 2 weeks prior to Visit 1 to control symptoms. Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement). Exclusion Criteria: 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 transient ischemic attack in past 90 days prior to Visit 1 Acute decompensated HF (exacerbation of CHF) 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, 1245-0168) 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 systolic blood pressure (SBP) < 100 mmHg at Visit 1 or 2 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, severe obesity (body mass index ≥40.0 kg/m2), orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries) amputation with artificial limb without stable prosthesis function for the past 3 months Any condition that in the opinion of the investigator would contraindicate the assessment of 6MWT Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial. ICD implantation within 1 month prior to Visit 1 or planned during the course of the trial Implanted cardiac resynchronisation therapy (CRT) Treatment with i.v. iron therapy or erythropoietin (EPO) within 3 months prior to screening. Further exclusion criteria applies
Facility Information:
Facility Name
Mobile Heart Specialists, PC
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
The Center for Clinical Trials, Inc.
City
Saraland
State/Province
Alabama
ZIP/Postal Code
36571
Country
United States
Facility Name
California Heart Specialists
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92648
Country
United States
Facility Name
Manshadi Heart Institute, Inc
City
Stockton
State/Province
California
ZIP/Postal Code
95204
Country
United States
Facility Name
University of California Los Angeles
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Western Connecticut Health Network
City
Danbury
State/Province
Connecticut
ZIP/Postal Code
06810
Country
United States
Facility Name
Bio1 Clinical Research
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
Infinite Clinical Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
Advance Medical Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
Pharmacology Research, LLC
City
North Miami Beach
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
Palm Beach Gardens Research Center, LLC
City
Palm Beach Gardens
State/Province
Florida
ZIP/Postal Code
33410
Country
United States
Facility Name
East Coast Institute for Research, LLC
City
Saint Augustine
State/Province
Florida
ZIP/Postal Code
32086
Country
United States
Facility Name
Cozy Research LLC
City
Zephyrhills
State/Province
Florida
ZIP/Postal Code
33541
Country
United States
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Georgia Arrhythmia Consultants and Research Institute
City
Warner Robins
State/Province
Georgia
ZIP/Postal Code
31093
Country
United States
Facility Name
St Luke's Clinic - Idaho Cardiology Associates
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Northwest Heart Clinical Research, LLC
City
Arlington Heights
State/Province
Illinois
ZIP/Postal Code
60005
Country
United States
Facility Name
Clinical Investigation Specialists, Inc
City
Gurnee
State/Province
Illinois
ZIP/Postal Code
60031
Country
United States
Facility Name
Chicago Medical Research
City
Hazel Crest
State/Province
Illinois
ZIP/Postal Code
60429
Country
United States
Facility Name
Midwest Heart and Vascular Specialists
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
Facility Name
Grace Research, LLC
City
Bossier City
State/Province
Louisiana
ZIP/Postal Code
71111
Country
United States
Facility Name
Grace Research, LLC
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71107
Country
United States
Facility Name
Clinical Trials of America LA, LLC
City
West Monroe
State/Province
Louisiana
ZIP/Postal Code
71291
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
John D. Dingell VA Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Med Research One
City
Florissant
State/Province
Missouri
ZIP/Postal Code
63031
Country
United States
Facility Name
Cox Medical Center South
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65807
Country
United States
Facility Name
The DOCS
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89113
Country
United States
Facility Name
Rutgers Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Albany Stratton VA Medical Center Albany, NY
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
UNC REX Healthcare
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
PMG Research of Rocky Mount, LLC
City
Rocky Mount
State/Province
North Carolina
ZIP/Postal Code
27804
Country
United States
Facility Name
PMG Research of Wilmington, LLC
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Rama Research LLC
City
Marion
State/Province
Ohio
ZIP/Postal Code
43302
Country
United States
Facility Name
Columbia Heart Clinic
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Black Hills Cardiovascular Research
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
The Jackson Clinic, PA
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38301
Country
United States
Facility Name
DiscoveResearch, Inc.
City
Beaumont
State/Province
Texas
ZIP/Postal Code
77701
Country
United States
Facility Name
Angiocardiac Care of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77025
Country
United States
Facility Name
Acacia Medical Research Institute,LLC
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77478
Country
United States
Facility Name
Mary Washington Hospital Research Department
City
Fredericksburg
State/Province
Virginia
ZIP/Postal Code
22401
Country
United States
Facility Name
York Clinical Research, LLC
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
Canberra Hospital
City
Garran
State/Province
Australian Capital Territory
ZIP/Postal Code
2605
Country
Australia
Facility Name
University of the Sunshine Coast
City
Birtinya
State/Province
Queensland
ZIP/Postal Code
4575
Country
Australia
Facility Name
Peninsular Health CV Research Unit
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
KMH Cardiology Centres Inc.
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5K 2L3
Country
Canada
Facility Name
Toronto Heart Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4P 1E4
Country
Canada
Facility Name
Sameh Fikry Medicine Professional Corporation
City
Waterloo
State/Province
Ontario
ZIP/Postal Code
N2J 1C4
Country
Canada
Facility Name
CIMS Studienzentrum Bamberg GmbH
City
Bamberg
ZIP/Postal Code
96049
Country
Germany
Facility Name
Klinische Forschung Berlin GbR
City
Berlin
ZIP/Postal Code
10787
Country
Germany
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Cardiologicum Dresden und Pirna
City
Dresden
ZIP/Postal Code
01277
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
IKF Pneumologie GmbH & Co. KG
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitätsklinikum Köln (AöR)
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitätsklinikum Magdeburg AöR
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
General Hospital of Athens Konstantopoulio-Agia Olga
City
Athens
ZIP/Postal Code
14233
Country
Greece
Facility Name
General Hospital of Athens "G. Gennimatas"
City
Athens
ZIP/Postal Code
15669
Country
Greece
Facility Name
General Hospital of Chalkida
City
Chalkida
ZIP/Postal Code
34100
Country
Greece
Facility Name
University General Hospital of Heraklion
City
Herakleion, Crete
ZIP/Postal Code
71110
Country
Greece
Facility Name
Univ. Gen. Hosp. of Ioannina
City
Ioannina
ZIP/Postal Code
45500
Country
Greece
Facility Name
University Hospital of Thessaloniki AHEPA
City
Thessaloniki
ZIP/Postal Code
54636
Country
Greece
Facility Name
Centro Cardiologico Monzino-IRCCS
City
Milano
ZIP/Postal Code
20138
Country
Italy
Facility Name
Asst Santi Paolo E Carlo
City
Milano
ZIP/Postal Code
20142
Country
Italy
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Ospedale Regina Montis Regalis
City
Mondovì (CN)
ZIP/Postal Code
12084
Country
Italy
Facility Name
Università Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Università degli studi di Palermo
City
Palermo
ZIP/Postal Code
90133
Country
Italy
Facility Name
IRCCS San Raffaele
City
Roma
ZIP/Postal Code
00163
Country
Italy
Facility Name
Sykehuset Østfold Kalnes
City
Grålum
ZIP/Postal Code
N-1714
Country
Norway
Facility Name
Oslo Universitetssykehus HF, Rikshospitalet
City
Oslo
ZIP/Postal Code
N-0372
Country
Norway
Facility Name
Helse Stavanger, Stavanger Universitetssykehus
City
Stavanger
ZIP/Postal Code
N-4011
Country
Norway
Facility Name
St. Olavs Hospital, Universitetssykehuset i Trondheim
City
Trondheim
ZIP/Postal Code
N-7030
Country
Norway
Facility Name
INTERCORE Medical Center
City
Bydgoszcz
ZIP/Postal Code
85-605
Country
Poland
Facility Name
10.Military Clin.Hospital&Polyclinic
City
Bydgoszcz
ZIP/Postal Code
85681
Country
Poland
Facility Name
Leszek Bryniarski Specialized Medical Cabinet
City
Krakow
ZIP/Postal Code
30-082
Country
Poland
Facility Name
Card.Cli.Mil.Med.Ac.Uni.Cli.Hosp. Cent.Vetera.Hosp.Lodz
City
Lodz
ZIP/Postal Code
91-425
Country
Poland
Facility Name
Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard
City
Lodz
ZIP/Postal Code
92-213
Country
Poland
Facility Name
Provincial Specialist M. Kopernik Hospital
City
Lodz
ZIP/Postal Code
93-513
Country
Poland
Facility Name
Independent Public Healthcare, Dept. of Cardiology, Pulawy
City
Pulawy
ZIP/Postal Code
24100
Country
Poland
Facility Name
Central Hospital of Medical Academy, Warsaw
City
Warsaw
ZIP/Postal Code
02-097
Country
Poland
Facility Name
4. Military Clinical Hospital with Polyclinic SP ZOZ
City
Wroclaw
ZIP/Postal Code
50 981
Country
Poland
Facility Name
CHLO, EPE - Hospital de Santa Cruz
City
Carnaxide
ZIP/Postal Code
2795
Country
Portugal
Facility Name
CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
City
Coimbra
ZIP/Postal Code
3041-801
Country
Portugal
Facility Name
Centro Hosp. de Leiria-Pombal
City
Leiria
ZIP/Postal Code
2410-197
Country
Portugal
Facility Name
CHLC, EPE - Hospital de Santa Marta
City
Lisboa
ZIP/Postal Code
1169-024
Country
Portugal
Facility Name
CHLO, EPE - Hospital S. Francisco Xavier
City
Lisboa
ZIP/Postal Code
1449-005
Country
Portugal
Facility Name
CHULN, EPE - Hospital de Santa Maria
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Facility Name
Centro Hospitalar Universitário São João,EPE
City
Porto
ZIP/Postal Code
4200-319
Country
Portugal
Facility Name
Hospital General Universitario de Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital San Rafael
City
Granada
ZIP/Postal Code
18001
Country
Spain
Facility Name
Hospital de la Inmaculada Concepción
City
Granada
ZIP/Postal Code
18004
Country
Spain
Facility Name
Hospital Universitario Virgen de las Nieves
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
Hospital La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Clínico de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Sahlgrenska US, Göteborg
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Sahlgrenska Universitetssjukhuset, Östra
City
Göteborg
ZIP/Postal Code
416 85
Country
Sweden
Facility Name
Skånes universitetssjukhus, Lund
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Akardo Med Site
City
Stockholm
ZIP/Postal Code
11446
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
34397263
Citation
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. Erratum In: Circulation. 2022 Feb 22;145(8):e641.
Results Reference
derived
PubMed Identifier
31218819
Citation
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.
Results Reference
derived
PubMed Identifier
31081589
Citation
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.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info

Learn more about this trial

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

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