This Study Tests Empagliflozin in Patients With Chronic H... | NCT03448419

ID	Type	Description	Link
2017-004073-14	EudraCT Number

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
Empagliflozin	Experimental		Drug: Empagliflozin
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Empagliflozin	Drug	Film-coated tablet	Empagliflozin	JARDIANCE, JARDIANZ, GIBTULIO

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)	Change from baseline in KCCQ-TSS was defined as the endpoint value at week 12 minus the last available measurement before start of treatment with randomised study medication. The KCCQ is 23 item self-administered questionnaire and comprises 7 domains: physical limitation, symptom frequency, symptom burden, symptom stability, social limitation, self-efficacy and quality of life. Additionally 3 summary scores exist: TSS, clinical summary score, and overall summary score. The scores of the KCCQ domains and summary scores range from 0 to 100, with higher score indicating better outcome. If no questionnaire was available at week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above. If no questionnaire was available at baseline, change from baseline was not imputed.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Of full age of consent (according to local legislation, usually ≥ 18 years) at screening.
Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
Signed and dated written informed consent in accordance with ICHGCP and local legislation prior to admission to the trial
6MWT distance ≤350 m at screening and at baseline.
Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in NYHA class II-IV
Chronic HF with reduced EF defined as LVEF ≤ 40 % as per echocardiography at Visit 1 as per local reading (obtained under stable condition).
Elevated NT-proBNP > 450 pg/ml for patients without atrial fibrillation (AF) OR NTproBNP > 600 pg/ml for patients with AF as analysed at the Central laboratory at Visit 1
Patients must be clinically stable and on appropriate and stable dose of medical therapy for HF (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine), consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at least two weeks prior to Visit 1. The investigator must document the reason in case the patient is not on such medication or if not on target dose of any heart failure medication as per local guidelines.
Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement).
Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, and if a device is required, it must have been implanted for at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD.

Exclusion Criteria:

Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to Visit 1
Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 4 weeks prior to Visit 1, and/or during screening period until Visit 2
Previous or current randomisation in another Empagliflozin Heart Failure trial (i.e. studies 1245.110, 1245.121, 1245-0167)
Type 1 Diabetes Mellitus (T1DM)
Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2 (CKD-EPIcr) or requiring dialysis, as determined at Visit 1
Symptomatic hypotension or a SBP < 100 mmHg at Visit 1 or 2
Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 1 or 2, or SBP >160mmHg at both Visit 1 and 2
Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 1 (Screening)
Unstable angina pectoris in past 30 days prior to Visit 1
Largest distance walked in 6 minutes (6MWTD) at baseline <100m.
Any presence of condition that precludes exercise testing such as:
- claudication,
- uncontrolled (according to investigator judgement) bradyarrhythmia or tachyarrhythmia,
- significant musculoskeletal disease,
- primary pulmonary hypertension,
- severe obesity (body mass index ≥40.0 kg/m2),
- orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries)
- amputation with artificial limb without stable prosthesis function for the past 3 months
- Any condition that, in the opinion of the investigator, would contraindicate the assessment of 6MWT
Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial.
Planned implantation of ICD or CRT during the course of the trial.
Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening
Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening
Further exclusion criteria applies

Facility	Status	City	State	ZIP	Country	Contacts
Mobile Heart Specialists, PC		Mobile	Alabama	36608	United States
The Center for Clinical Trials, Inc.

PubMed Identifier	Type	Citation	Retractions
34397263	Derived	Anker SD, Ponikowski P, Wanner C, Pfarr E, Hauske S, Peil B, Salsali A, Ritter I, Koitka-Weber A, Brueckmann M, Lindenfeld J, Abraham WT; EMPERIAL Investigators and National Coordinators. Kidney Function After Initiation and Discontinuation of Empagliflozin in Patients With Heart Failure With and Without Type 2 Diabetes: Insights From the EMPERIAL Trials. Circulation. 2021 Oct 12;144(15):1265-1267. doi: 10.1161/CIRCULATIONAHA.121.054669. Epub 2021 Aug 16. No abstract available.
31218819

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
FG001	10 mg Empagliflozin

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Oct 21, 2019	Sep 28, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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

Randomised Set: All participants that were randomised, regardless of whether treated or not.

Posted

Median

Inter-Quartile Range

Meter (m)

At baseline and at week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Units	Counts
Participants	OG000156 OG001156

Title

Denominators

Categories

Title	Measurements
	OG00018.0(-11.5 to 54.0) OG00113.5(-8.0 to 42.0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	H0: There is no difference between the effect of placebo and the effect of empagliflozin.	Wilcoxon rank test, normal approximation		0.4236		Median difference (HL-estimate)	-4.0			2-Sided	95	-16.0	6.0			Empagliflozin vs. Placebo. For estimation of effect, the non-parametric Hodge-Lehman (HL) estimate for the median difference was calculated.		Superiority

Secondary

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

Change from baseline in KCCQ-TSS was defined as the endpoint value at week 12 minus the last available measurement before start of treatment with randomised study medication. The KCCQ is 23 item self-administered questionnaire and comprises 7 domains: physical limitation, symptom frequency, symptom burden, symptom stability, social limitation, self-efficacy and quality of life. Additionally 3 summary scores exist: TSS, clinical summary score, and overall summary score. The scores of the KCCQ domains and summary scores range from 0 to 100, with higher score indicating better outcome. If no questionnaire was available at week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above. If no questionnaire was available at baseline, change from baseline was not imputed.

Randomised Set: All participants that were randomised, regardless of whether treated or not.

Posted

Median

Inter-Quartile Range

Score on a scale

At baseline and at week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin

Secondary

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

Change from baseline in CHQ-SAS was defined as the endpoint value at week 12 minus the last available endpoint value before start of treatment with randomised study medication. The CHQ-SAS evaluates 3 domains: dyspnoea, fatigue, and emotional function. Scores of the domains range from 1 to 7, with higher score indicating better quality of life. If no questionnaire was available at week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above. If no questionnaire was available at baseline, change from baseline was not imputed.

Participants in the randomised set (RS) who have no missing values at baseline.

Posted

Median

95% Confidence Interval

Score on scale

At baseline and at week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Secondary

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

Change from baseline to week 6 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. Change from baseline was defined as the distance walked in 6 minutes at week 6 minus the baseline value. Baseline value was defined as the last available measurement before start of treatment with randomised study medication.

If a participant was present at the visit at week 6 but did not perform the 6MWT, the participant was evaluated as having walked a distance of 0 meter. If no value was available for week 6, an imputed value was used.

Randomised Set: All participants that were randomised, regardless of whether treated or not.

Posted

Median

Inter-Quartile Range

Meter (m)

At baseline and at week 6

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Secondary

Change From Baseline to Week 12 in Clinical Congestion Score

Change from baseline to week 12 in Clinical Congestion score is defined as the score-value at week 12 minus the score-value at baseline. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. The Clinical Congestion Score (summary score) is based on 3 items: orthopnoea, jugular venous distention (JVD) and oedema. Each item was assessed through a 4-measure questionnaire, which was further converted to a standardised 4-point scale ranging from 0 to 3, with 0 indicating no or fewer symptoms and 3 indicating continous or more symptoms. If at least 2 of the 3 items are not missing, the summary score is calculated as: (average over items JVD, orthopnea and oedema actually answered)*3. The summary score range from 0 to 9, with lower value indicating better health, and higher value indicating worse health. Mean is adjusted mean.

Only participants in the randomised set (RS) who have baseline and at least one post-baseline value.

Posted

Mean

Standard Error

Score on a scale

At baseline and at week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Secondary

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

Change from baseline to week 12 in PGI-S of Heart Failure Symptoms. The Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of symptoms severity, specifically: shortness of breath, fatigue and swelling. The PGI-S asks the Patient to choose one response that best describes how his/her heart failure symptoms, specifically: shortness of breath, fatigue and swelling are now on a 5-point scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.

Only participants in the randomised set (RS) who have values at baseline and at week 12.

Posted

Count of Participants

Participants

At baseline and at week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Secondary

Change From Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) of Dyspnoea

Change from baseline to week 12 in Patient Global Impression of Severity (PGI-S) of dyspnoea. The PGI-S of Dyspnoea is a 1-item questionnaire designed to assess the participant´s impression of symptom severity, specifically dyspnoea. The PGI-S item asks the participant to choose one response that best describes how his/her dyspnoea is now on a 5-point scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.

Only participants in the randomised set (RS) who have values at baseline and at week 12.

Posted

Count of Participants

Participants

At baseline and at week 12

ID	Title	Description
OG000	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Secondary

Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12

The Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of change in heart failure symptoms, specifically: shortness of breath, fatigue, and swelling. The PGI-C asks the patient to choose one Response that best describes the overall change (if any) in his/her heart failure symptoms, specifically: shortness of breath, fatigue, and swelling since he/she started taking the study medication on a 7- category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).

Only participants in the randomised set (RS) who have week 12 value.

Posted

Count of Participants

Participants

At week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Secondary

Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12

The PGI-C in Dyspnoea is a 1-item questionnaire designed to assess the patient's Impression of change in dyspnoea. The PGI-C asks the patient to choose one response that best describes the change (if any) in his/her shortness of breath when performing usual activities since he/she started taking the study medication on a 7-category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).

Only participants in the randomised set (RS) who have week 12 value.

Posted

Count of Participants

Participants

At week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Units	Counts
Participants

Secondary

Relative Change From Baseline to Week 12 in N-terminal Pro-brain Natriuretic Peptide (NTproBNP)

Relative change from baseline to week 12 in N-terminal pro-brain natriuretic peptide (NTproBNP). Relative change from baseline is expressed as ratio of week 12 to baseline. Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication.

Only participants in the randomised set (RS) who have baseline and at least one baseline value.

Posted

Mean

95% Confidence Interval

Ratio

Within 3 weeks prior to treatment start and at Week 12

ID	Title	Description
OG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
OG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Angina pectoris	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Angina unstable	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Cardiac failure	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG00012 affected156 at risk EG0016 affected155 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Myocardial infarction	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Oedema peripheral	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Liver injury	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Bronchitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Osteomyelitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Parotitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Pneumonia	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0012 affected155 at risk
Respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Septic shock	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Vulval abscess	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0011 affected155 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0012 affected155 at risk
Dizziness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0011 affected155 at risk
Epilepsy	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Somnolence	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Syncope	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Device malfunction	Product Issues	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0011 affected155 at risk
Bladder cyst	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Renal failure	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Renal injury	Renal and urinary disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0011 affected155 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Subcutaneous emphysema	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Hypertensive urgency	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0001 affected156 at risk EG0010 affected155 at risk
Hypotension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 affected156 at risk EG0012 affected155 at risk

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
BG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	1 film-coated tablet of Placebo matching empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).	3	156	27	156	0	156
EG001	10 mg Empagliflozin	1 film-coated tablet of 10 milligram (mg) of Empagliflozin was administered orally once daily for 12 weeks in participants with chronic Heart Failure (CHF) with reduced left ventricular ejection fraction (LVEF≤40%).	3	155	21	155	0	155