search
Back to results

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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Empagliflozin
Placebo to Empagliflozin
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:

  • 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)
  • Further Inclusion Criteria Apply

Exclusion Criteria:

  • 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)
  • Further Exclusion Criteria Apply

Sites / Locations

  • University of Southern California
  • Cedars-Sinai Medical Center
  • University of California Irvine
  • The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Cardiology Associates Research Co.
  • University of Florida Health Jacksonville
  • Grady Memorial Hospital
  • Methodist Medical Center
  • Beth Israel Deaconess Medical Center
  • United Hospital
  • University Of Mississippi Medical Center
  • Saint Luke's Hospital of Kansas City
  • University of Nebraska Medical Center
  • Cardiovascular Associates of the Delaware Valley
  • Jefferson Washington Township Hospital
  • Montefiore Medical Center
  • Erie County Medical Center
  • The DeMatteis Center for Cardiac Research and Education
  • Stony Brook Medicine
  • The University of North Carolina at Chapel Hill
  • North Carolina Heart and Vascular
  • University of Oklahoma
  • South Oklahoma Heart Research Group
  • Ralph H. Johnson VA Medical Center
  • Vanderbilt University Medical Center
  • Pharmatex Research
  • Center for Advanced Cardiac Care - Heart Failure Clinic
  • Inova Fairfax Medical Campus
  • Sentara Norfolk General Hospital
  • University of Wisconsin
  • Aalst - HOSP Onze-Lieve-Vrouw
  • Brussels - UNIV UZ Brussel
  • AZ Sint-Blasius
  • Ziekenhuis Oost-Limburg - Campus Sint-Jan
  • UZ Leuven
  • Liège - HOSP CHR de la Citadelle
  • UNIV Ambroise Paré
  • Royal Jubilee Hospital
  • St. Boniface General Hospital
  • Toronto General Hospital
  • Beijing Chao-Yang Hospital
  • Beijing AnZhen Hospital
  • The First Hospital of Jilin University
  • West China Hospital
  • Xiamen Cardiovascular Hospital Xiamen University
  • First Affiliated Hospital of Xi'an JiaoTong University
  • University Hospital Brno
  • Univ.Hosp U Svate Anny, I.Internal Clinic-Cardiology,Brno
  • University Hospital Motol
  • District Hospital, Tabor
  • Aalborg Universitetsshospital
  • Frederiksberg Hospital
  • Herlev and Gentofte Hospital
  • Hvidovre Hospital
  • Viborg Regionhospital
  • Charité - Universitätsmedizin Berlin
  • Bremer Institut für Herz- und Kreislaufforschung (BIHKF) am Klinikum Links der Weser
  • Herzzentrum Dresden GmbH Universitätsklinik
  • Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH
  • Universitätsklinikum Gießen und Marburg GmbH
  • Universitätsklinikum Jena
  • Asklepios Klinik Langen-Seligenstadt GmbH
  • Klinikum Leverkusen gGmbH, Leverkusen
  • Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Universitätsklinikum Würzburg AÖR
  • Semmelweis University
  • University Debrecen Hospital
  • University of Pecs
  • Fejer County Saint George University Teaching Hospital
  • Csongrad Country Dr Bugyi Istvan Hosp.
  • ASST degli Spedali Civili di Brescia
  • Università degli Studi "Magna Grecia" - Campus "S. Venuta"
  • Ospedale della Val di Chiana Santa Margherita
  • Az.Osp. Universitaria "Ospedali Riuniti"
  • Centro Cardiologico Monzino-IRCCS
  • ASST Grande Ospedale Metropolitano Niguarda
  • Osp. Guglielmo da Saliceto AUSL di Piacenza
  • IRCCS San Raffaele
  • AO Città della Salute e della
  • Azienda Sanitaria Universitaria Giuliano Isontina
  • Japan Community Health Care Organization Kyushu Hospital
  • Mito Medical Center
  • Kanagawa Cardiovascular and Respiratory Center
  • Shinshu University Hospital
  • The Sakakibara Heart Institute of Okayama
  • Osaka University Hospital
  • Kawaguchi Cardiovascular and Respiratory Hospital
  • Saitama Sekishikai Hospital
  • Nihon University Itabashi Hospital
  • Jeroen Bosch Ziekenhuis-Hertogenbosch
  • Gelre Ziekenhuizen Apeldoorn
  • HagaZiekenhuis
  • TREANT Zorggroep
  • Groene Hart ziekenhuis
  • Universitair Medisch Centrum Groningen
  • Sint Jansdal Ziekenhuis
  • Alrijne Leiderdorp
  • Bravis ziekenhuis, locatie Roosendaal
  • Diakonessenhuis Utrecht
  • Helse Førde HF, Førde Sentralsjukehus
  • Sykehuset Innlandet HF, Avd. Lillehammer
  • Akershus Universitetssykehus HF
  • Helse Stavanger, Stavanger Universitetssykehus
  • Universitetssykehuset Nord-Norge, Tromsø
  • Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia
  • Card.Cli.Mil.Med.Ac.Uni.Cli.Hosp. Cent.Vetera.Hosp.Lodz
  • Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard
  • Provincial Specialist M. Kopernik Hospital
  • Hospital Universitario Virgen de la Arrixaca
  • Hospital de Bellvitge
  • Hospital Puerta de Hierro
  • Hospital Virgen de la Victoria
  • Hospital Moises Broggi
  • Hospital Nuestra Señora de Valme
  • Hospital Clínico de Valencia
  • Sahlgrenska US, Göteborg
  • Sahlgrenska Universitetssjukhuset, Östra

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Empagliflozin

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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: Death: death is worse than no death; earlier death is worse; tied if not possible to determine. Number of HFEs: more HFEs is worse; tied, if same number of HFEs. Time to first HFE: earlier HFE is worse; tied, if not possible to determine. 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

Secondary Outcome Measures

Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment
Number of participants with improvement of at least 10 points in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS) from baseline after 90 days of treatment. The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire that includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. The symptom frequency and symptom burden domains are merged into the total symptom score. Scores are represented on a 0-to-100-point scale, where a higher score reflects a better health status.
Change From Baseline in KCCQ-TSS After 90 Days of Treatment
Change from baseline in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS). The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire that includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. The symptom frequency and symptom burden domains are merged into the total symptom score. The score is represented on a 0-to-100-point scale, where a higher score reflects a better health status. Change from baseline in KCCQ-TSS at day 90 was modeled using a MMRM with visit (day 15 and day 30) as repeated measures, adjusted mean (standard error) after 90 days of treatment is reported.
Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment
Change from baseline in log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area under the curve (AUC) over 30 days of treatment is reported.
Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge
The follow-up time for DAOH analyses was defined as 30 days after initial hospital discharge, or time between initial hospital discharge and date of censoring for non-fatal events except for patients who died within the first 30 days, where 30 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 30 days after initial hospital discharge as well as the number of days being dead within the 30 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100.
Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation
The follow-up time for DAOH analyses was defined as 90 days after randomisation, or time between randomisation and date of censoring for non-fatal events except for patients who died within the first 90 days, where 90 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 90 days after randomisation as well as the number of days being dead within the first 90 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100.
Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit
Incidence rate of first occurrence of CV death or HFE until end of trial visit per 100 patient-year (pt-yrs) at risk is reported. Incidence rate per 100 pt-yrs = 100* number of patients with event / time at risk [years].
Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge
Number of participants with hospitalization for heart failure (HHF) until 30 days after initial hospital discharge.
Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr
The occurrence of the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), or 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) from baseline of ≥40%, or sustained eGFR [mL/min/1.73 m2] <15 and baseline value ≥30, or sustained eGFR <10 and baseline value <30; is reported by number of participants with component events. (These events may have occurred after the endpoint was already met. Combinations may not have occurred on the same day). Sustained was determined by 2 or more consecutive post-baseline central laboratory measurements separated by at least 30 days.
Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment
Diuretic effect as assessed by weight change per mean daily loop diuretic dose after 15 days of treatment. Diuretic dose = 40 mg intravenous furosemide or 80 mg oral furosemide. Abbreviation: Kg: Kilogram
Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment
Diuretic effect as assessed by weight change per mean daily loop diuretic dose after 30 days of treatment. Diuretic dose = 40 mg intravenous furosemide or 80 mg oral furosemide Abbreviation: Kg: Kilogram

Full Information

First Posted
November 4, 2019
Last Updated
June 28, 2022
Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
search

1. Study Identification

Unique Protocol Identification Number
NCT04157751
Brief Title
A Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure
Official Title
A Multicentre, Randomised, Double-blind, 90-day Superiority Trial to Evaluate the Effect on Clinical Benefit, Safety and Tolerability of Once Daily Oral EMPagliflozin 10 mg Compared to Placebo, Initiated in Patients Hospitalised for acUte Heart faiLure (de Novo or Decompensated Chronic HF) Who Have Been StabilisEd (EMPULSE)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
May 18, 2020 (Actual)
Primary Completion Date
May 28, 2021 (Actual)
Study Completion Date
June 2, 2021 (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
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.

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
530 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Intervention Description
Film-coated tablet
Intervention Type
Drug
Intervention Name(s)
Placebo to Empagliflozin
Intervention Description
Film-coated tablet
Primary Outcome Measure Information:
Title
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
Description
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: Death: death is worse than no death; earlier death is worse; tied if not possible to determine. Number of HFEs: more HFEs is worse; tied, if same number of HFEs. Time to first HFE: earlier HFE is worse; tied, if not possible to determine. 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
Time Frame
Up to 90 days. For KCCQ-TSS: at baseline and at day 90.
Secondary Outcome Measure Information:
Title
Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment
Description
Number of participants with improvement of at least 10 points in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS) from baseline after 90 days of treatment. The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire that includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. The symptom frequency and symptom burden domains are merged into the total symptom score. Scores are represented on a 0-to-100-point scale, where a higher score reflects a better health status.
Time Frame
At baseline and at day 90.
Title
Change From Baseline in KCCQ-TSS After 90 Days of Treatment
Description
Change from baseline in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS). The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire that includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. The symptom frequency and symptom burden domains are merged into the total symptom score. The score is represented on a 0-to-100-point scale, where a higher score reflects a better health status. Change from baseline in KCCQ-TSS at day 90 was modeled using a MMRM with visit (day 15 and day 30) as repeated measures, adjusted mean (standard error) after 90 days of treatment is reported.
Time Frame
At baseline, at day 15, 30 and at day 90.
Title
Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment
Description
Change from baseline in log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area under the curve (AUC) over 30 days of treatment is reported.
Time Frame
From baseline to day 30.
Title
Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge
Description
The follow-up time for DAOH analyses was defined as 30 days after initial hospital discharge, or time between initial hospital discharge and date of censoring for non-fatal events except for patients who died within the first 30 days, where 30 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 30 days after initial hospital discharge as well as the number of days being dead within the 30 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100.
Time Frame
Up to 30 days after initial hospital discharge.
Title
Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation
Description
The follow-up time for DAOH analyses was defined as 90 days after randomisation, or time between randomisation and date of censoring for non-fatal events except for patients who died within the first 90 days, where 90 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 90 days after randomisation as well as the number of days being dead within the first 90 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100.
Time Frame
Up to 90 days after randomisation.
Title
Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit
Description
Incidence rate of first occurrence of CV death or HFE until end of trial visit per 100 patient-year (pt-yrs) at risk is reported. Incidence rate per 100 pt-yrs = 100* number of patients with event / time at risk [years].
Time Frame
Up to 127 days.
Title
Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge
Description
Number of participants with hospitalization for heart failure (HHF) until 30 days after initial hospital discharge.
Time Frame
Up to 30 days after initial hospital discharge.
Title
Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr
Description
The occurrence of the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), or 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) from baseline of ≥40%, or sustained eGFR [mL/min/1.73 m2] <15 and baseline value ≥30, or sustained eGFR <10 and baseline value <30; is reported by number of participants with component events. (These events may have occurred after the endpoint was already met. Combinations may not have occurred on the same day). Sustained was determined by 2 or more consecutive post-baseline central laboratory measurements separated by at least 30 days.
Time Frame
Up to 90 days.
Title
Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment
Description
Diuretic effect as assessed by weight change per mean daily loop diuretic dose after 15 days of treatment. Diuretic dose = 40 mg intravenous furosemide or 80 mg oral furosemide. Abbreviation: Kg: Kilogram
Time Frame
At baseline and at day 15.
Title
Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment
Description
Diuretic effect as assessed by weight change per mean daily loop diuretic dose after 30 days of treatment. Diuretic dose = 40 mg intravenous furosemide or 80 mg oral furosemide Abbreviation: Kg: Kilogram
Time Frame
At baseline and at day 30.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Further Inclusion Criteria Apply Exclusion Criteria: 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) Further Exclusion Criteria Apply
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of California Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92865
Country
United States
Facility Name
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Cardiology Associates Research Co.
City
Daytona Beach
State/Province
Florida
ZIP/Postal Code
32117
Country
United States
Facility Name
University of Florida Health Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Methodist Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61603
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
United Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
University Of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4505
Country
United States
Facility Name
Saint Luke's Hospital of Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Cardiovascular Associates of the Delaware Valley
City
Elmer
State/Province
New Jersey
ZIP/Postal Code
08318
Country
United States
Facility Name
Jefferson Washington Township Hospital
City
Washington Township
State/Province
New Jersey
ZIP/Postal Code
08080
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Erie County Medical Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
The DeMatteis Center for Cardiac Research and Education
City
Greenvale
State/Province
New York
ZIP/Postal Code
11548
Country
United States
Facility Name
Stony Brook Medicine
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
North Carolina Heart and Vascular
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
University of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
South Oklahoma Heart Research Group
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73135
Country
United States
Facility Name
Ralph H. Johnson VA Medical Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Pharmatex Research
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79109
Country
United States
Facility Name
Center for Advanced Cardiac Care - Heart Failure Clinic
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
Inova Fairfax Medical Campus
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Sentara Norfolk General Hospital
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Aalst - HOSP Onze-Lieve-Vrouw
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Brussels - UNIV UZ Brussel
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
AZ Sint-Blasius
City
Dendermonde
ZIP/Postal Code
9200
Country
Belgium
Facility Name
Ziekenhuis Oost-Limburg - Campus Sint-Jan
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Liège - HOSP CHR de la Citadelle
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
UNIV Ambroise Paré
City
Mons
ZIP/Postal Code
7000
Country
Belgium
Facility Name
Royal Jubilee Hospital
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8R 1J8
Country
Canada
Facility Name
St. Boniface General Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Beijing Chao-Yang Hospital
City
Beijing
ZIP/Postal Code
100020
Country
China
Facility Name
Beijing AnZhen Hospital
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
The First Hospital of Jilin University
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
West China Hospital
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Xiamen Cardiovascular Hospital Xiamen University
City
Xiamen
ZIP/Postal Code
361004
Country
China
Facility Name
First Affiliated Hospital of Xi'an JiaoTong University
City
Xian
ZIP/Postal Code
710061
Country
China
Facility Name
University Hospital Brno
City
Brno
ZIP/Postal Code
639 00
Country
Czechia
Facility Name
Univ.Hosp U Svate Anny, I.Internal Clinic-Cardiology,Brno
City
Brno
ZIP/Postal Code
65691
Country
Czechia
Facility Name
University Hospital Motol
City
Prag
ZIP/Postal Code
15006
Country
Czechia
Facility Name
District Hospital, Tabor
City
Tabor
ZIP/Postal Code
390 03
Country
Czechia
Facility Name
Aalborg Universitetsshospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Frederiksberg Hospital
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
Facility Name
Herlev and Gentofte Hospital
City
Herlev
ZIP/Postal Code
2733
Country
Denmark
Facility Name
Hvidovre Hospital
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Facility Name
Viborg Regionhospital
City
Viborg
ZIP/Postal Code
8800
Country
Denmark
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Bremer Institut für Herz- und Kreislaufforschung (BIHKF) am Klinikum Links der Weser
City
Bremen
ZIP/Postal Code
28277
Country
Germany
Facility Name
Herzzentrum Dresden GmbH Universitätsklinik
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitätsklinikum Gießen und Marburg GmbH
City
Gießen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Universitätsklinikum Jena
City
Jena
ZIP/Postal Code
07743
Country
Germany
Facility Name
Asklepios Klinik Langen-Seligenstadt GmbH
City
Langen
ZIP/Postal Code
63225
Country
Germany
Facility Name
Klinikum Leverkusen gGmbH, Leverkusen
City
Leverkusen
ZIP/Postal Code
51375
Country
Germany
Facility Name
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
City
Ludwigshafen
ZIP/Postal Code
67063
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
Universitätsklinikum Würzburg AÖR
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
University Debrecen Hospital
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
University of Pecs
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Fejer County Saint George University Teaching Hospital
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Csongrad Country Dr Bugyi Istvan Hosp.
City
Szentes
ZIP/Postal Code
6600
Country
Hungary
Facility Name
ASST degli Spedali Civili di Brescia
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Università degli Studi "Magna Grecia" - Campus "S. Venuta"
City
Catanzaro
ZIP/Postal Code
88100
Country
Italy
Facility Name
Ospedale della Val di Chiana Santa Margherita
City
Cortona
ZIP/Postal Code
52040
Country
Italy
Facility Name
Az.Osp. Universitaria "Ospedali Riuniti"
City
Foggia
ZIP/Postal Code
71100
Country
Italy
Facility Name
Centro Cardiologico Monzino-IRCCS
City
Milano
ZIP/Postal Code
20138
Country
Italy
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Osp. Guglielmo da Saliceto AUSL di Piacenza
City
Piacenza
ZIP/Postal Code
29121
Country
Italy
Facility Name
IRCCS San Raffaele
City
Roma
ZIP/Postal Code
00163
Country
Italy
Facility Name
AO Città della Salute e della
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Azienda Sanitaria Universitaria Giuliano Isontina
City
Trieste
ZIP/Postal Code
34124
Country
Italy
Facility Name
Japan Community Health Care Organization Kyushu Hospital
City
Fukuoka, Kitakyushu
ZIP/Postal Code
806-8501
Country
Japan
Facility Name
Mito Medical Center
City
Ibaraki, Higashiibaraki-gun
ZIP/Postal Code
311-3193
Country
Japan
Facility Name
Kanagawa Cardiovascular and Respiratory Center
City
Kanagawa, Yokohama
ZIP/Postal Code
236-0051
Country
Japan
Facility Name
Shinshu University Hospital
City
Nagano, Matsumoto
ZIP/Postal Code
390-8621
Country
Japan
Facility Name
The Sakakibara Heart Institute of Okayama
City
Okayama, Okayama
ZIP/Postal Code
700-0804
Country
Japan
Facility Name
Osaka University Hospital
City
Osaka, Suita
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Kawaguchi Cardiovascular and Respiratory Hospital
City
Saitama, Kawaguchi
ZIP/Postal Code
333-0842
Country
Japan
Facility Name
Saitama Sekishikai Hospital
City
Saitama, Sayama
ZIP/Postal Code
350-1305
Country
Japan
Facility Name
Nihon University Itabashi Hospital
City
Tokyo, Itabashi-ku
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Jeroen Bosch Ziekenhuis-Hertogenbosch
City
's HERTOGENBOSCH
ZIP/Postal Code
5223 GZ
Country
Netherlands
Facility Name
Gelre Ziekenhuizen Apeldoorn
City
Apeldoorn
ZIP/Postal Code
7334 DZ
Country
Netherlands
Facility Name
HagaZiekenhuis
City
Den Haag
ZIP/Postal Code
2545 AA
Country
Netherlands
Facility Name
TREANT Zorggroep
City
Emmen
ZIP/Postal Code
7824 AA
Country
Netherlands
Facility Name
Groene Hart ziekenhuis
City
Gouda
ZIP/Postal Code
2803 HH
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Sint Jansdal Ziekenhuis
City
Harderwijk
ZIP/Postal Code
3844 DG
Country
Netherlands
Facility Name
Alrijne Leiderdorp
City
Leiderdorp
ZIP/Postal Code
2353 GA
Country
Netherlands
Facility Name
Bravis ziekenhuis, locatie Roosendaal
City
Roosendaal
ZIP/Postal Code
4708 AE
Country
Netherlands
Facility Name
Diakonessenhuis Utrecht
City
Utrecht
ZIP/Postal Code
3582 KE
Country
Netherlands
Facility Name
Helse Førde HF, Førde Sentralsjukehus
City
Førde
ZIP/Postal Code
N-6812
Country
Norway
Facility Name
Sykehuset Innlandet HF, Avd. Lillehammer
City
Lillehammer
ZIP/Postal Code
N-2609
Country
Norway
Facility Name
Akershus Universitetssykehus HF
City
Lørenskog
ZIP/Postal Code
N-1478
Country
Norway
Facility Name
Helse Stavanger, Stavanger Universitetssykehus
City
Stavanger
ZIP/Postal Code
N-4011
Country
Norway
Facility Name
Universitetssykehuset Nord-Norge, Tromsø
City
Tromsø
ZIP/Postal Code
N-9019
Country
Norway
Facility Name
Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia
City
Gdynia
ZIP/Postal Code
81348
Country
Poland
Facility Name
Card.Cli.Mil.Med.Ac.Uni.Cli.Hosp. Cent.Vetera.Hosp.Lodz
City
Lodz
ZIP/Postal Code
90549
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
Hospital Universitario Virgen de la Arrixaca
City
El Palmar
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital de Bellvitge
City
L'Hospitalet de Llobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Virgen de la Victoria
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Moises Broggi
City
Sant Joan Despi
ZIP/Postal Code
08970
Country
Spain
Facility Name
Hospital Nuestra Señora de Valme
City
Sevilla
ZIP/Postal Code
41014
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
41345
Country
Sweden
Facility Name
Sahlgrenska Universitetssjukhuset, Östra
City
Göteborg
ZIP/Postal Code
416 85
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
IPD Sharing 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.
IPD Sharing 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'.
IPD Sharing URL
https://www.mystudywindow.com/msw/datasharing
Citations:
PubMed Identifier
35377706
Citation
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.
Results Reference
derived
PubMed Identifier
35228754
Citation
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.
Results Reference
derived
Links:
URL
http://www.mystudywindow.com
Description
Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs