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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04157751
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 530
• Locations: 118
• Arms: 2
• Actual Duration (Months): 12.5
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Empagliflozin; Drug: Placebo to Empagliflozin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 530 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 18, 2020
• Actual Primary Completion Date: May 28, 2021
• Actual Study Completion Date: Jun 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Empagliflozin	Drug: Empagliflozin; Film-coated tablet
Placebo Comparator: Placebo	Drug: Placebo to Empagliflozin; Film-coated tablet

Outcome Measures

Primary Outcome Measures

1. Percentage of Pairwise Comparisons With Wins of Clinical Benefit, a Composite of Death, Number of Heart Failure Events (HFEs), Time to the First HFE and ≥5-point Difference in CfB in KCCQ-TSS After 90 Days of Treatment [Up to 90 days. For KCCQ-TSS: at baseline and at day 90.]

   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

1. Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment [At baseline and at day 90.]

   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.

2. Change From Baseline in KCCQ-TSS After 90 Days of Treatment [At baseline, at day 15, 30 and at day 90.]

   Change from baseline in 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.

3. Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment [From baseline to day 30.]

   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.

4. Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge [Up to 30 days after initial hospital discharge.]

   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.

5. Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation [Up to 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.

6. Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit [Up to 127 days.]

   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].

7. Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge [Up to 30 days after initial hospital discharge.]

   Number of participants with hospitalization for heart failure (HHF) until 30 days after initial hospital discharge.

8. Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr [Up to 90 days.]

   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.

9. Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment [At baseline and at day 15.]

   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

10. Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment [At baseline and at day 30.]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	University of California Irvine	Orange	California	United States	92865
4	The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California	United States	90502
5	Cardiology Associates Research Co.	Daytona Beach	Florida	United States	32117
6	University of Florida Health Jacksonville	Jacksonville	Florida	United States	32209
7	Grady Memorial Hospital	Atlanta	Georgia	United States	30303
8	Methodist Medical Center	Peoria	Illinois	United States	61603
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	United Hospital	Saint Paul	Minnesota	United States	55102
11	University Of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
12	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
13	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
14	Cardiovascular Associates of the Delaware Valley	Elmer	New Jersey	United States	08318
15	Jefferson Washington Township Hospital	Washington Township	New Jersey	United States	08080
16	Montefiore Medical Center	Bronx	New York	United States	10467
17	Erie County Medical Center	Buffalo	New York	United States	14215
18	The DeMatteis Center for Cardiac Research and Education	Greenvale	New York	United States	11548
19	Stony Brook Medicine	Stony Brook	New York	United States	11794
20	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
21	North Carolina Heart and Vascular	Raleigh	North Carolina	United States	27607
22	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
23	South Oklahoma Heart Research Group	Oklahoma City	Oklahoma	United States	73135
24	Ralph H. Johnson VA Medical Center	Charleston	South Carolina	United States	29401
25	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
26	Pharmatex Research	Amarillo	Texas	United States	79109
27	Center for Advanced Cardiac Care - Heart Failure Clinic	Plano	Texas	United States	75093
28	Inova Fairfax Medical Campus	Falls Church	Virginia	United States	22042
29	Sentara Norfolk General Hospital	Norfolk	Virginia	United States	23507
30	University of Wisconsin	Madison	Wisconsin	United States	53792
31	Aalst - HOSP Onze-Lieve-Vrouw	Aalst		Belgium	9300
32	Brussels - UNIV UZ Brussel	Brussel		Belgium	1090
33	AZ Sint-Blasius	Dendermonde		Belgium	9200
34	Ziekenhuis Oost-Limburg - Campus Sint-Jan	Genk		Belgium	3600
35	UZ Leuven	Leuven		Belgium	3000
36	Liège - HOSP CHR de la Citadelle	Liège		Belgium	4000
37	UNIV Ambroise Paré	Mons		Belgium	7000
38	Royal Jubilee Hospital	Victoria	British Columbia	Canada	V8R 1J8
39	St. Boniface General Hospital	Winnipeg	Manitoba	Canada	R2H 2A6
40	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
41	Beijing Chao-Yang Hospital	Beijing		China	100020
42	Beijing AnZhen Hospital	Beijing		China	100029
43	The First Hospital of Jilin University	Changchun		China	130021
44	West China Hospital	Chengdu		China	610041
45	Xiamen Cardiovascular Hospital Xiamen University	Xiamen		China	361004
46	First Affiliated Hospital of Xi'an JiaoTong University	Xian		China	710061
47	University Hospital Brno	Brno		Czechia	639 00
48	Univ.Hosp U Svate Anny, I.Internal Clinic-Cardiology,Brno	Brno		Czechia	65691
49	University Hospital Motol	Prag		Czechia	15006
50	District Hospital, Tabor	Tabor		Czechia	390 03
51	Aalborg Universitetsshospital	Aalborg		Denmark	9000
52	Frederiksberg Hospital	Frederiksberg		Denmark	2000
53	Herlev and Gentofte Hospital	Herlev		Denmark	2733
54	Hvidovre Hospital	Hvidovre		Denmark	2650
55	Viborg Regionhospital	Viborg		Denmark	8800
56	Charité - Universitätsmedizin Berlin	Berlin		Germany	12203
57	Bremer Institut für Herz- und Kreislaufforschung (BIHKF) am Klinikum Links der Weser	Bremen		Germany	28277
58	Herzzentrum Dresden GmbH Universitätsklinik	Dresden		Germany	01307
59	Universitäts-Herzzentrum Freiburg, Bad Krozingen GmbH	Freiburg		Germany	79106
60	Universitätsklinikum Gießen und Marburg GmbH	Gießen		Germany	35392
61	Universitätsklinikum Jena	Jena		Germany	07743
62	Asklepios Klinik Langen-Seligenstadt GmbH	Langen		Germany	63225
63	Klinikum Leverkusen gGmbH, Leverkusen	Leverkusen		Germany	51375
64	Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen		Germany	67063
65	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck		Germany	23538
66	Universitätsklinikum Würzburg AÖR	Würzburg		Germany	97080
67	Semmelweis University	Budapest		Hungary	1088
68	University Debrecen Hospital	Debrecen		Hungary	4032
69	University of Pecs	Pecs		Hungary	7624
70	Fejer County Saint George University Teaching Hospital	Szekesfehervar		Hungary	8000
71	Csongrad Country Dr Bugyi Istvan Hosp.	Szentes		Hungary	6600
72	ASST degli Spedali Civili di Brescia	Brescia		Italy	25123
73	Università degli Studi "Magna Grecia" - Campus "S. Venuta"	Catanzaro		Italy	88100
74	Ospedale della Val di Chiana Santa Margherita	Cortona		Italy	52040
75	Az.Osp. Universitaria "Ospedali Riuniti"	Foggia		Italy	71100
76	Centro Cardiologico Monzino-IRCCS	Milano		Italy	20138
77	ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
78	Osp. Guglielmo da Saliceto AUSL di Piacenza	Piacenza		Italy	29121
79	IRCCS San Raffaele	Roma		Italy	00163
80	AO Città della Salute e della	Torino		Italy	10126
81	Azienda Sanitaria Universitaria Giuliano Isontina	Trieste		Italy	34124
82	Japan Community Health Care Organization Kyushu Hospital	Fukuoka, Kitakyushu		Japan	806-8501
83	Mito Medical Center	Ibaraki, Higashiibaraki-gun		Japan	311-3193
84	Kanagawa Cardiovascular and Respiratory Center	Kanagawa, Yokohama		Japan	236-0051
85	Shinshu University Hospital	Nagano, Matsumoto		Japan	390-8621
86	The Sakakibara Heart Institute of Okayama	Okayama, Okayama		Japan	700-0804
87	Osaka University Hospital	Osaka, Suita		Japan	565-0871
88	Kawaguchi Cardiovascular and Respiratory Hospital	Saitama, Kawaguchi		Japan	333-0842
89	Saitama Sekishikai Hospital	Saitama, Sayama		Japan	350-1305
90	Nihon University Itabashi Hospital	Tokyo, Itabashi-ku		Japan	173-8610
91	Jeroen Bosch Ziekenhuis-Hertogenbosch	's HERTOGENBOSCH		Netherlands	5223 GZ
92	Gelre Ziekenhuizen Apeldoorn	Apeldoorn		Netherlands	7334 DZ
93	HagaZiekenhuis	Den Haag		Netherlands	2545 AA
94	TREANT Zorggroep	Emmen		Netherlands	7824 AA
95	Groene Hart ziekenhuis	Gouda		Netherlands	2803 HH
96	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
97	Sint Jansdal Ziekenhuis	Harderwijk		Netherlands	3844 DG
98	Alrijne Leiderdorp	Leiderdorp		Netherlands	2353 GA
99	Bravis ziekenhuis, locatie Roosendaal	Roosendaal		Netherlands	4708 AE
100	Diakonessenhuis Utrecht	Utrecht		Netherlands	3582 KE
101	Helse Førde HF, Førde Sentralsjukehus	Førde		Norway	N-6812
102	Sykehuset Innlandet HF, Avd. Lillehammer	Lillehammer		Norway	N-2609
103	Akershus Universitetssykehus HF	Lørenskog		Norway	N-1478
104	Helse Stavanger, Stavanger Universitetssykehus	Stavanger		Norway	N-4011
105	Universitetssykehuset Nord-Norge, Tromsø	Tromsø		Norway	N-9019
106	Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia	Gdynia		Poland	81348
107	Card.Cli.Mil.Med.Ac.Uni.Cli.Hosp. Cent.Vetera.Hosp.Lodz	Lodz		Poland	90549
108	Cent.Clin.Hosp.Med.Univ.Lodz,Electrocard	Lodz		Poland	92-213
109	Provincial Specialist M. Kopernik Hospital	Lodz		Poland	93-513
110	Hospital Universitario Virgen de la Arrixaca	El Palmar		Spain	30120
111	Hospital de Bellvitge	L'Hospitalet de Llobregat		Spain	08907
112	Hospital Puerta de Hierro	Majadahonda		Spain	28222
113	Hospital Virgen de la Victoria	Malaga		Spain	29010
114	Hospital Moises Broggi	Sant Joan Despi		Spain	08970
115	Hospital Nuestra Señora de Valme	Sevilla		Spain	41014
116	Hospital Clínico de Valencia	Valencia		Spain	46010
117	Sahlgrenska US, Göteborg	Göteborg		Sweden	41345
118	Sahlgrenska Universitetssjukhuset, Östra	Göteborg		Sweden	416 85

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 4, 2020
• Statistical Analysis Plan - Mar 11, 2021

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04157751
• Other Study ID Numbers: 1245-0204; 2019-002946-19
• First Posted: Nov 8, 2019
• Last Update Posted: Jul 19, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Heart Failure; Empagliflozin

Study Results

Participant Flow

Recruitment Details	A multicentre, randomised, double-blind trial to assess whether in-hospital administration of empagliflozin results in improvement in heart failure-related outcomes compared to placebo in patients with acute heart failure.
Pre-assignment Detail	All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Period Title: Overall Study
STARTED	265	265
Treated	264	260
COMPLETED	202	208
NOT COMPLETED	63	57

Baseline Characteristics

Arm/Group Title	Placebo	10 mg Empagliflozin	Total
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.	Total of all reporting groups
Overall Participants	265	265	530
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.1 (13.8)	68.9 (12.6)	68.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	93 35.1%	86 32.5%	179 33.8%
Male	172 64.9%	179 67.5%	351 66.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 3.4%	6 2.3%	15 2.8%
Not Hispanic or Latino	256 96.6%	259 97.7%	515 97.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.8%	0 0%	2 0.4%
Asian	25 9.4%	32 12.1%	57 10.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	33 12.5%	21 7.9%	54 10.2%
White	202 76.2%	211 79.6%	413 77.9%
More than one race	2 0.8%	1 0.4%	3 0.6%
Unknown or Not Reported	1 0.4%	0 0%	1 0.2%
Kansas City cardiomyopathy questionnaire-Total symptom score (KCCQ-TSS) (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	41.91 (23.98)	39.71 (24.06)	40.81 (24.02)

Outcome Measures

1. Primary Outcome

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.

Outcome Measure Data

Analysis Population Description

Randomised Set (RS), including all randomised patients.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	265	265
Measure Pairwise comparisons	39162	39162
Time to death	4.01	7.15
Frequency of HFEs	7.65	10.59
Time to HFE	0.57	0.24
KCCQ-TSS change from baseline (>=5-point difference)	27.48	35.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Empagliflozin
	Comments	Stratified win ratio (WR) was used, calculated as total number of wins in the empa group across all strata divided by total number of losses. Weights were applied analogous to a Mantel-Haenszel approach. death in pbo first; death in empa first; HFEs in pbo more frequently; HFEs in empa more frequently; HFEs in pbo first; HFEs in empa first; KCCQ-TSS change lower in pbo; KCCQ-TSS change lower in empa
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments	p-value for WR<=1.0 (one-sided), variance calculated using the asymptotic normal U statistics approach.
	Method	Asymptotic normal U statistics approach
	Comments
Method of Estimation	Estimation Parameter	Stratified Win Ratio
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	WR estimate= [((a)+(c)+(e)+(g)) / ((b)+(d)+(f)+(h))]

2. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Randomised Set (RS), including all randomised patients.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	265	265
Count of Participants [Participants]	202 76.2%	220 83%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Empagliflozin
	Comments	Logistic regression including terms for baseline KCCQ-TSS, treatment and heart failure status
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0970
	Comments	p-value for OR=1.0 (two-sided).
	Method	Regression, Logistic
	Comments	Wald Confidence interval.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.522
	Confidence Interval	(2-Sided) 95%; 0.927 to 2.501
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.386
	Estimation Comments	Comparison vs. Placebo.

3. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patients in the randomised set (RS) and with non-missing data for this endpoint. Observed case including data after treatment discontinuation (OC-AD).

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	221	230
Least Squares Mean (Standard Error) [Score on a scale]	31.73 (1.49)	36.19 (1.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Empagliflozin
	Comments	Restricted maximum likelihood estimation based on a mixed-effect model for repeated measures (MMRM) analysis to obtain adjusted means for the treatment effects. This model included discrete fixed effects for treatment group, and heart failure status at each visit and continuous fixed effects for baseline value at each visit. Missing data caused by patient withdrawal or other reasons were handled implicitly by the MMRM approach. Unstructured covariance structure was used.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0347
	Comments	p-value for difference = 0 (two-sided)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference of adjusted mean
	Estimated Value	4.45
	Confidence Interval	(2-Sided) 95%; 0.32 to 8.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.10
	Estimation Comments

4. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patients included the randomised set (RS), and with non-missing data for this endpoint.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	256	255
Geometric Least Squares Mean (95% Confidence Interval) [Picogram/milliliter * days]	26.77	24.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Empagliflozin
	Comments	Area under the curve (AUC) of change from baseline in log-transformed NT-proBNP level over 30 days of treatment was analysed by an analysis of covariance (ANCOVA). NT-proBNP level is regarded as log-normally distributed, therefore values were log-transformed prior to analysis. The linear trapezoidal rule was used to calculate the AUC after the log-transformation had been applied to each value.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0176
	Comments
	Method	ANCOVA
	Comments	ANCOVA with a discrete fixed effect for heart failure status and a continuous fixed effect for baseline NT-proBNP level.
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.82 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison vs. Placebo

5. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patients included the treated set (TS), and with non-missing data for this endpoint. TS includes all patients treated with at least one dose of trial medication.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	264	258
Mean (Standard Deviation) [DAOH in percentage (%)]	80.90 (21.25)	81.37 (18.62)

6. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patients in the treated set (TS) and with non-missing data for this endpoint.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	260	257
Mean (Standard Deviation) [DAOH in percentage (%)]	85.79 (22.76)	87.55 (19.54)

7. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Randomised Set (RS), including all randomised patients.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	265	265
Number (95% Confidence Interval) [Patients with events / 100pt-yrs at risk]	78.81	55.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg Empagliflozin
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1241
	Comments	p-value for HR=1.0 (two sided)
	Method	Regression, Cox
	Comments	Cox proportional hazard model with terms for heart failure status and treatment.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison vs. Placebo.

8. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Randomised Set (RS), including all randomised patients.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	265	265
Count of Participants [Participants]	12 4.5%	14 5.3%

9. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Randomised Set (RS), including all randomised patients.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	265	265
Count of Participants [Participants]	2 0.8%	0 0%

10. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patients in the randomised set (RS) and with non-missing values for this endpoint.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	224	212
Mean (Standard Deviation) [Kg per loop diuretic dose]	-2.43 (23.46)	-4.45 (16.65)

11. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

Patients in the randomised set (RS) and with non-missing values for this endpoint.

Arm/Group Title	Placebo	10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.	1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
Measure Participants	216	219
Mean (Standard Deviation) [Kg per loop diuretic dose]	-2.69 (21.74)	-6.91 (25.34)

Adverse Events

Time Frame	[All-cause Mortality]: From first study drug intake until end of follow-up, up to 202 days. [Serious and Other Adverse Event]: From first study drug intake until 7 days after last intake of study medication, up to 127 days.
Adverse Event Reporting Description	[All-cause Mortality]: Randomised Set (RS) including all randomised patients. [Serious and Other Adverse Events]: Treated Set (TS), consisting of all patients treated with at least once dose of trial medication.
Arm/Group Title	Placebo		10 mg Empagliflozin
Arm/Group Description	1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure.		1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure.
All Cause Mortality
	Placebo		10 mg Empagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/265 (8.3%)		11/265 (4.2%)
Serious Adverse Events
	Placebo		10 mg Empagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/264 (43.6%)		84/260 (32.3%)
Cardiac disorders
Acute left ventricular failure	2/264 (0.8%)		0/260 (0%)
Acute myocardial infarction	1/264 (0.4%)		0/260 (0%)
Aortic valve incompetence	1/264 (0.4%)		0/260 (0%)
Atrial fibrillation	2/264 (0.8%)		3/260 (1.2%)
Atrial flutter	2/264 (0.8%)		1/260 (0.4%)
Atrial thrombosis	1/264 (0.4%)		1/260 (0.4%)
Bradycardia	0/264 (0%)		3/260 (1.2%)
Cardiac arrest	5/264 (1.9%)		2/260 (0.8%)
Cardiac failure	37/264 (14%)		25/260 (9.6%)
Cardiac failure acute	3/264 (1.1%)		3/260 (1.2%)
Cardiac failure chronic	2/264 (0.8%)		2/260 (0.8%)
Cardiac failure congestive	11/264 (4.2%)		2/260 (0.8%)
Cardiac ventricular thrombosis	0/264 (0%)		1/260 (0.4%)
Cardiogenic shock	1/264 (0.4%)		1/260 (0.4%)
Chronic left ventricular failure	3/264 (1.1%)		1/260 (0.4%)
Coronary artery disease	0/264 (0%)		2/260 (0.8%)
Coronary artery occlusion	2/264 (0.8%)		0/260 (0%)
Coronary artery stenosis	0/264 (0%)		2/260 (0.8%)
Coronary ostial stenosis	1/264 (0.4%)		0/260 (0%)
Mitral valve incompetence	1/264 (0.4%)		1/260 (0.4%)
Myocardial infarction	3/264 (1.1%)		0/260 (0%)
Myocardial ischaemia	0/264 (0%)		1/260 (0.4%)
Silent myocardial infarction	1/264 (0.4%)		0/260 (0%)
Sinus node dysfunction	1/264 (0.4%)		1/260 (0.4%)
Ventricular arrhythmia	1/264 (0.4%)		0/260 (0%)
Ventricular fibrillation	1/264 (0.4%)		0/260 (0%)
Ventricular tachycardia	7/264 (2.7%)		8/260 (3.1%)
Congenital, familial and genetic disorders
Gastrointestinal arteriovenous malformation	1/264 (0.4%)		0/260 (0%)
Ear and labyrinth disorders
Deafness	1/264 (0.4%)		0/260 (0%)
Gastrointestinal disorders
Abdominal pain	0/264 (0%)		1/260 (0.4%)
Ascites	0/264 (0%)		1/260 (0.4%)
Colitis ischaemic	0/264 (0%)		1/260 (0.4%)
Constipation	0/264 (0%)		1/260 (0.4%)
Gastrointestinal haemorrhage	0/264 (0%)		1/260 (0.4%)
Ileus	1/264 (0.4%)		1/260 (0.4%)
Intestinal ischaemia	1/264 (0.4%)		1/260 (0.4%)
Intestinal obstruction	0/264 (0%)		1/260 (0.4%)
Mesenteric arteriosclerosis	0/264 (0%)		1/260 (0.4%)
Obstructive pancreatitis	1/264 (0.4%)		0/260 (0%)
Pancreatitis acute	1/264 (0.4%)		0/260 (0%)
Small intestinal obstruction	1/264 (0.4%)		0/260 (0%)
General disorders
Death	2/264 (0.8%)		2/260 (0.8%)
Multiple organ dysfunction syndrome	1/264 (0.4%)		0/260 (0%)
Pyrexia	1/264 (0.4%)		0/260 (0%)
Sudden cardiac death	1/264 (0.4%)		0/260 (0%)
Vascular stent stenosis	0/264 (0%)		1/260 (0.4%)
Hepatobiliary disorders
Acute hepatic failure	1/264 (0.4%)		0/260 (0%)
Cholecystitis	1/264 (0.4%)		0/260 (0%)
Congestive hepatopathy	2/264 (0.8%)		0/260 (0%)
Hepatic cirrhosis	1/264 (0.4%)		0/260 (0%)
Hepatotoxicity	0/264 (0%)		1/260 (0.4%)
Infections and infestations
Bacterial infection	1/264 (0.4%)		0/260 (0%)
COVID-19	3/264 (1.1%)		1/260 (0.4%)
COVID-19 pneumonia	2/264 (0.8%)		1/260 (0.4%)
Erysipelas	0/264 (0%)		1/260 (0.4%)
Hepatitis A	1/264 (0.4%)		0/260 (0%)
Infection	1/264 (0.4%)		0/260 (0%)
Infectious pleural effusion	0/264 (0%)		1/260 (0.4%)
Infective exacerbation of chronic obstructive airways disease	1/264 (0.4%)		0/260 (0%)
Intervertebral discitis	1/264 (0.4%)		0/260 (0%)
Klebsiella infection	1/264 (0.4%)		0/260 (0%)
Pelvic abscess	0/264 (0%)		1/260 (0.4%)
Pneumonia	4/264 (1.5%)		0/260 (0%)
Pulmonary sepsis	1/264 (0.4%)		0/260 (0%)
Sepsis	2/264 (0.8%)		0/260 (0%)
Septic shock	1/264 (0.4%)		1/260 (0.4%)
Staphylococcal bacteraemia	1/264 (0.4%)		0/260 (0%)
Subcutaneous abscess	1/264 (0.4%)		0/260 (0%)
Urinary tract infection	0/264 (0%)		1/260 (0.4%)
Urinary tract infection bacterial	2/264 (0.8%)		0/260 (0%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	0/264 (0%)		1/260 (0.4%)
Dislocation of vertebra	1/264 (0.4%)		0/260 (0%)
Eye injury	0/264 (0%)		1/260 (0.4%)
Fall	0/264 (0%)		3/260 (1.2%)
Femur fracture	1/264 (0.4%)		0/260 (0%)
Fibula fracture	1/264 (0.4%)		0/260 (0%)
Head injury	0/264 (0%)		1/260 (0.4%)
Humerus fracture	0/264 (0%)		1/260 (0.4%)
Ligament sprain	1/264 (0.4%)		0/260 (0%)
Subdural haematoma	1/264 (0.4%)		0/260 (0%)
Tibia fracture	1/264 (0.4%)		0/260 (0%)
Vascular pseudoaneurysm	1/264 (0.4%)		0/260 (0%)
Investigations
Blood creatinine increased	1/264 (0.4%)		1/260 (0.4%)
Blood urea increased	0/264 (0%)		1/260 (0.4%)
Blood uric acid increased	0/264 (0%)		1/260 (0.4%)
Glomerular filtration rate decreased	1/264 (0.4%)		0/260 (0%)
International normalised ratio increased	1/264 (0.4%)		0/260 (0%)
Troponin increased	1/264 (0.4%)		0/260 (0%)
Metabolism and nutrition disorders
Dehydration	0/264 (0%)		1/260 (0.4%)
Electrolyte imbalance	0/264 (0%)		1/260 (0.4%)
Gout	1/264 (0.4%)		0/260 (0%)
Hyperglycaemia	1/264 (0.4%)		0/260 (0%)
Hyperkalaemia	1/264 (0.4%)		2/260 (0.8%)
Hypoglycaemia	1/264 (0.4%)		1/260 (0.4%)
Hypokalaemia	1/264 (0.4%)		0/260 (0%)
Metabolic acidosis	1/264 (0.4%)		1/260 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma	0/264 (0%)		1/260 (0.4%)
Meningioma	0/264 (0%)		1/260 (0.4%)
Metastases to bone	1/264 (0.4%)		0/260 (0%)
Metastatic neoplasm	2/264 (0.8%)		0/260 (0%)
Prostate cancer	1/264 (0.4%)		0/260 (0%)
Prostate cancer metastatic	1/264 (0.4%)		0/260 (0%)
Nervous system disorders
Carotid artery dissection	1/264 (0.4%)		0/260 (0%)
Carotid artery occlusion	1/264 (0.4%)		0/260 (0%)
Cauda equina syndrome	1/264 (0.4%)		0/260 (0%)
Cerebrovascular accident	3/264 (1.1%)		3/260 (1.2%)
Monoplegia	1/264 (0.4%)		0/260 (0%)
Paraplegia	1/264 (0.4%)		0/260 (0%)
Speech disorder	1/264 (0.4%)		0/260 (0%)
Spinal cord compression	1/264 (0.4%)		0/260 (0%)
Syncope	0/264 (0%)		1/260 (0.4%)
Toxic encephalopathy	0/264 (0%)		1/260 (0.4%)
Transient ischaemic attack	0/264 (0%)		1/260 (0.4%)
Psychiatric disorders
Delirium	1/264 (0.4%)		1/260 (0.4%)
Mental status changes	1/264 (0.4%)		1/260 (0.4%)
Suicide attempt	1/264 (0.4%)		0/260 (0%)
Renal and urinary disorders
Acute kidney injury	19/264 (7.2%)		10/260 (3.8%)
Chronic kidney disease	3/264 (1.1%)		0/260 (0%)
Hydronephrosis	1/264 (0.4%)		0/260 (0%)
Nephropathy	1/264 (0.4%)		0/260 (0%)
Nephrotic syndrome	1/264 (0.4%)		0/260 (0%)
Renal artery stenosis	0/264 (0%)		1/260 (0.4%)
Renal impairment	4/264 (1.5%)		2/260 (0.8%)
Urinary retention	0/264 (0%)		1/260 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	3/264 (1.1%)		0/260 (0%)
Acute respiratory failure	3/264 (1.1%)		1/260 (0.4%)
Asthma	0/264 (0%)		1/260 (0.4%)
Chronic obstructive pulmonary disease	2/264 (0.8%)		1/260 (0.4%)
Dyspnoea	2/264 (0.8%)		2/260 (0.8%)
Epistaxis	1/264 (0.4%)		0/260 (0%)
Haemothorax	1/264 (0.4%)		0/260 (0%)
Pleural effusion	1/264 (0.4%)		1/260 (0.4%)
Pulmonary embolism	3/264 (1.1%)		1/260 (0.4%)
Pulmonary hypertension	1/264 (0.4%)		0/260 (0%)
Pulmonary oedema	3/264 (1.1%)		0/260 (0%)
Respiratory failure	1/264 (0.4%)		1/260 (0.4%)
Rhinitis allergic	1/264 (0.4%)		0/260 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/264 (0%)		1/260 (0.4%)
Vascular disorders
Deep vein thrombosis	1/264 (0.4%)		1/260 (0.4%)
Extremity necrosis	0/264 (0%)		1/260 (0.4%)
Hypertensive crisis	2/264 (0.8%)		0/260 (0%)
Hypertensive emergency	1/264 (0.4%)		0/260 (0%)
Hypotension	5/264 (1.9%)		2/260 (0.8%)
Hypovolaemic shock	1/264 (0.4%)		0/260 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		10 mg Empagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/264 (7.2%)		20/260 (7.7%)
Vascular disorders
Hypotension	19/264 (7.2%)		20/260 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.