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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04157751
Recruitment Status : Completed
First Posted : November 8, 2019
Results First Posted : June 6, 2022
Last Update Posted : July 19, 2022
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Empagliflozin
Drug: Placebo to Empagliflozin
Enrollment 530
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 Details 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
Hide 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 [1] 265 265
Treated 264 260
Completed 202 208
Not Completed 63 57
Reason Not Completed
Withdrawal by Subject             12             17
Lost to Follow-up             6             2
Adverse Event             34             23
Not treated             1             5
Other reason not stated above             10             10
[1]
Randomised
Arm/Group Title Placebo 10 mg Empagliflozin Total
Hide 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 Number of Baseline Participants 265 265 530
Hide Baseline Analysis Population Description
Randomised Set (RS), including all randomised patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 265 participants 265 participants 530 participants
68.1  (13.8) 68.9  (12.6) 68.5  (13.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 265 participants 265 participants 530 participants
Female
93
  35.1%
86
  32.5%
179
  33.8%
Male
172
  64.9%
179
  67.5%
351
  66.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 265 participants 265 participants 530 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%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 265 participants 265 participants 530 participants
American Indian or Alaska Native
2
   0.8%
0
   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%
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
   0.0%
1
   0.2%
Kansas City cardiomyopathy questionnaire-Total symptom score (KCCQ-TSS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 264 participants 262 participants 526 participants
41.91  (23.98) 39.71  (24.06) 40.81  (24.02)
[1]
Measure Description: 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 a total symptom score. Scores are represented on a 0-to-100-point scale, where a higher score reflects a better health status. KCCQ-TSS at baseline is reported. Only participants in the randomised set and with non-missing data are included.
[2]
Measure Analysis Population Description: Only participants in the randomised set and with non-missing data are included.
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
Hide 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:

  1. Death: death is worse than no death; earlier death is worse; tied if not possible to determine.
  2. Number of HFEs: more HFEs is worse; tied, if same number of HFEs.
  3. Time to first HFE: earlier HFE is worse; tied, if not possible to determine.
  4. 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS), including all randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 265 265
Overall Number of Units Analyzed
Type of Units Analyzed: Pairwise comparisons
39162 39162
Measure Type: Number
Unit of Measure: pct. (%) of winning pairwise comparisons
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
Hide 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.

  1. death in pbo first;
  2. death in empa first;
  3. HFEs in pbo more frequently;
  4. HFEs in empa more frequently;
  5. HFEs in pbo first;
  6. HFEs in empa first;
  7. KCCQ-TSS change lower in pbo;
  8. KCCQ-TSS change lower in empa
Type of Statistical Test Other
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter Stratified Win Ratio
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
1.09 to 1.68
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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS), including all randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 265 265
Measure Type: Count of Participants
Unit of Measure: Participants
202
  76.2%
220
  83.0%
Hide 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 [Not Specified]
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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 221 230
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
31.73  (1.49) 36.19  (1.48)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0347
Comments p-value for difference = 0 (two-sided)
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients included the randomised set (RS), and with non-missing data for this endpoint.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 256 255
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: Picogram/milliliter * days
26.77
(25.15 to 28.48)
24.07
(22.61 to 25.62)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0176
Comments [Not Specified]
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
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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 264 258
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the treated set (TS) and with non-missing data for this endpoint.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 260 257
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS), including all randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 265 265
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events / 100pt-yrs at risk
78.81
(58.11 to 102.62)
55.01
(38.10 to 74.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 10 mg Empagliflozin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
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
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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS), including all randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 265 265
Measure Type: Count of Participants
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS), including all randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 265 265
Measure Type: Count of Participants
Unit of Measure: Participants
2
   0.8%
0
   0.0%
10.Secondary Outcome
Title Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the randomised set (RS) and with non-missing values for this endpoint.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 224 212
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the randomised set (RS) and with non-missing values for this endpoint.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide 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.
Overall Number of Participants Analyzed 216 219
Mean (Standard Deviation)
Unit of Measure: Kg per loop diuretic dose
-2.69  (21.74) -6.91  (25.34)
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
Hide 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 (%) Affected / at Risk (%)
Total   22/265 (8.30%)   11/265 (4.15%) 
Hide Serious Adverse Events
Placebo 10 mg Empagliflozin
Affected / at Risk (%) Affected / at Risk (%)
Total   115/264 (43.56%)   84/260 (32.31%) 
Cardiac disorders     
Acute left ventricular failure  1  2/264 (0.76%)  0/260 (0.00%) 
Acute myocardial infarction  1  1/264 (0.38%)  0/260 (0.00%) 
Aortic valve incompetence  1  1/264 (0.38%)  0/260 (0.00%) 
Atrial fibrillation  1  2/264 (0.76%)  3/260 (1.15%) 
Atrial flutter  1  2/264 (0.76%)  1/260 (0.38%) 
Atrial thrombosis  1  1/264 (0.38%)  1/260 (0.38%) 
Bradycardia  1  0/264 (0.00%)  3/260 (1.15%) 
Cardiac arrest  1  5/264 (1.89%)  2/260 (0.77%) 
Cardiac failure  1  37/264 (14.02%)  25/260 (9.62%) 
Cardiac failure acute  1  3/264 (1.14%)  3/260 (1.15%) 
Cardiac failure chronic  1  2/264 (0.76%)  2/260 (0.77%) 
Cardiac failure congestive  1  11/264 (4.17%)  2/260 (0.77%) 
Cardiac ventricular thrombosis  1  0/264 (0.00%)  1/260 (0.38%) 
Cardiogenic shock  1  1/264 (0.38%)  1/260 (0.38%) 
Chronic left ventricular failure  1  3/264 (1.14%)  1/260 (0.38%) 
Coronary artery disease  1  0/264 (0.00%)  2/260 (0.77%) 
Coronary artery occlusion  1  2/264 (0.76%)  0/260 (0.00%) 
Coronary artery stenosis  1  0/264 (0.00%)  2/260 (0.77%) 
Coronary ostial stenosis  1  1/264 (0.38%)  0/260 (0.00%) 
Mitral valve incompetence  1  1/264 (0.38%)  1/260 (0.38%) 
Myocardial infarction  1  3/264 (1.14%)  0/260 (0.00%) 
Myocardial ischaemia  1  0/264 (0.00%)  1/260 (0.38%) 
Silent myocardial infarction  1  1/264 (0.38%)  0/260 (0.00%) 
Sinus node dysfunction  1  1/264 (0.38%)  1/260 (0.38%) 
Ventricular arrhythmia  1  1/264 (0.38%)  0/260 (0.00%) 
Ventricular fibrillation  1  1/264 (0.38%)  0/260 (0.00%) 
Ventricular tachycardia  1  7/264 (2.65%)  8/260 (3.08%) 
Congenital, familial and genetic disorders     
Gastrointestinal arteriovenous malformation  1  1/264 (0.38%)  0/260 (0.00%) 
Ear and labyrinth disorders     
Deafness  1  1/264 (0.38%)  0/260 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/264 (0.00%)  1/260 (0.38%) 
Ascites  1  0/264 (0.00%)  1/260 (0.38%) 
Colitis ischaemic  1  0/264 (0.00%)  1/260 (0.38%) 
Constipation  1  0/264 (0.00%)  1/260 (0.38%) 
Gastrointestinal haemorrhage  1  0/264 (0.00%)  1/260 (0.38%) 
Ileus  1  1/264 (0.38%)  1/260 (0.38%) 
Intestinal ischaemia  1  1/264 (0.38%)  1/260 (0.38%) 
Intestinal obstruction  1  0/264 (0.00%)  1/260 (0.38%) 
Mesenteric arteriosclerosis  1  0/264 (0.00%)  1/260 (0.38%) 
Obstructive pancreatitis  1  1/264 (0.38%)  0/260 (0.00%) 
Pancreatitis acute  1  1/264 (0.38%)  0/260 (0.00%) 
Small intestinal obstruction  1  1/264 (0.38%)  0/260 (0.00%) 
General disorders     
Death  1  2/264 (0.76%)  2/260 (0.77%) 
Multiple organ dysfunction syndrome  1  1/264 (0.38%)  0/260 (0.00%) 
Pyrexia  1  1/264 (0.38%)  0/260 (0.00%) 
Sudden cardiac death  1  1/264 (0.38%)  0/260 (0.00%) 
Vascular stent stenosis  1  0/264 (0.00%)  1/260 (0.38%) 
Hepatobiliary disorders     
Acute hepatic failure  1  1/264 (0.38%)  0/260 (0.00%) 
Cholecystitis  1  1/264 (0.38%)  0/260 (0.00%) 
Congestive hepatopathy  1  2/264 (0.76%)  0/260 (0.00%) 
Hepatic cirrhosis  1  1/264 (0.38%)  0/260 (0.00%) 
Hepatotoxicity  1  0/264 (0.00%)  1/260 (0.38%) 
Infections and infestations     
Bacterial infection  1  1/264 (0.38%)  0/260 (0.00%) 
COVID-19  1  3/264 (1.14%)  1/260 (0.38%) 
COVID-19 pneumonia  1  2/264 (0.76%)  1/260 (0.38%) 
Erysipelas  1  0/264 (0.00%)  1/260 (0.38%) 
Hepatitis A  1  1/264 (0.38%)  0/260 (0.00%) 
Infection  1  1/264 (0.38%)  0/260 (0.00%) 
Infectious pleural effusion  1  0/264 (0.00%)  1/260 (0.38%) 
Infective exacerbation of chronic obstructive airways disease  1  1/264 (0.38%)  0/260 (0.00%) 
Intervertebral discitis  1  1/264 (0.38%)  0/260 (0.00%) 
Klebsiella infection  1  1/264 (0.38%)  0/260 (0.00%) 
Pelvic abscess  1  0/264 (0.00%)  1/260 (0.38%) 
Pneumonia  1  4/264 (1.52%)  0/260 (0.00%) 
Pulmonary sepsis  1  1/264 (0.38%)  0/260 (0.00%) 
Sepsis  1  2/264 (0.76%)  0/260 (0.00%) 
Septic shock  1  1/264 (0.38%)  1/260 (0.38%) 
Staphylococcal bacteraemia  1  1/264 (0.38%)  0/260 (0.00%) 
Subcutaneous abscess  1  1/264 (0.38%)  0/260 (0.00%) 
Urinary tract infection  1  0/264 (0.00%)  1/260 (0.38%) 
Urinary tract infection bacterial  1  2/264 (0.76%)  0/260 (0.00%) 
Injury, poisoning and procedural complications     
Cervical vertebral fracture  1  0/264 (0.00%)  1/260 (0.38%) 
Dislocation of vertebra  1  1/264 (0.38%)  0/260 (0.00%) 
Eye injury  1  0/264 (0.00%)  1/260 (0.38%) 
Fall  1  0/264 (0.00%)  3/260 (1.15%) 
Femur fracture  1  1/264 (0.38%)  0/260 (0.00%) 
Fibula fracture  1  1/264 (0.38%)  0/260 (0.00%) 
Head injury  1  0/264 (0.00%)  1/260 (0.38%) 
Humerus fracture  1  0/264 (0.00%)  1/260 (0.38%) 
Ligament sprain  1  1/264 (0.38%)  0/260 (0.00%) 
Subdural haematoma  1  1/264 (0.38%)  0/260 (0.00%) 
Tibia fracture  1  1/264 (0.38%)  0/260 (0.00%) 
Vascular pseudoaneurysm  1  1/264 (0.38%)  0/260 (0.00%) 
Investigations     
Blood creatinine increased  1  1/264 (0.38%)  1/260 (0.38%) 
Blood urea increased  1  0/264 (0.00%)  1/260 (0.38%) 
Blood uric acid increased  1  0/264 (0.00%)  1/260 (0.38%) 
Glomerular filtration rate decreased  1  1/264 (0.38%)  0/260 (0.00%) 
International normalised ratio increased  1  1/264 (0.38%)  0/260 (0.00%) 
Troponin increased  1  1/264 (0.38%)  0/260 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/264 (0.00%)  1/260 (0.38%) 
Electrolyte imbalance  1  0/264 (0.00%)  1/260 (0.38%) 
Gout  1  1/264 (0.38%)  0/260 (0.00%) 
Hyperglycaemia  1  1/264 (0.38%)  0/260 (0.00%) 
Hyperkalaemia  1  1/264 (0.38%)  2/260 (0.77%) 
Hypoglycaemia  1  1/264 (0.38%)  1/260 (0.38%) 
Hypokalaemia  1  1/264 (0.38%)  0/260 (0.00%) 
Metabolic acidosis  1  1/264 (0.38%)  1/260 (0.38%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung adenocarcinoma  1  0/264 (0.00%)  1/260 (0.38%) 
Meningioma  1  0/264 (0.00%)  1/260 (0.38%) 
Metastases to bone  1  1/264 (0.38%)  0/260 (0.00%) 
Metastatic neoplasm  1  2/264 (0.76%)  0/260 (0.00%) 
Prostate cancer  1  1/264 (0.38%)  0/260 (0.00%) 
Prostate cancer metastatic  1  1/264 (0.38%)  0/260 (0.00%) 
Nervous system disorders     
Carotid artery dissection  1  1/264 (0.38%)  0/260 (0.00%) 
Carotid artery occlusion  1  1/264 (0.38%)  0/260 (0.00%) 
Cauda equina syndrome  1  1/264 (0.38%)  0/260 (0.00%) 
Cerebrovascular accident  1  3/264 (1.14%)  3/260 (1.15%) 
Monoplegia  1  1/264 (0.38%)  0/260 (0.00%) 
Paraplegia  1  1/264 (0.38%)  0/260 (0.00%) 
Speech disorder  1  1/264 (0.38%)  0/260 (0.00%) 
Spinal cord compression  1  1/264 (0.38%)  0/260 (0.00%) 
Syncope  1  0/264 (0.00%)  1/260 (0.38%) 
Toxic encephalopathy  1  0/264 (0.00%)  1/260 (0.38%) 
Transient ischaemic attack  1  0/264 (0.00%)  1/260 (0.38%) 
Psychiatric disorders     
Delirium  1  1/264 (0.38%)  1/260 (0.38%) 
Mental status changes  1  1/264 (0.38%)  1/260 (0.38%) 
Suicide attempt  1  1/264 (0.38%)  0/260 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  19/264 (7.20%)  10/260 (3.85%) 
Chronic kidney disease  1  3/264 (1.14%)  0/260 (0.00%) 
Hydronephrosis  1  1/264 (0.38%)  0/260 (0.00%) 
Nephropathy  1  1/264 (0.38%)  0/260 (0.00%) 
Nephrotic syndrome  1  1/264 (0.38%)  0/260 (0.00%) 
Renal artery stenosis  1  0/264 (0.00%)  1/260 (0.38%) 
Renal impairment  1  4/264 (1.52%)  2/260 (0.77%) 
Urinary retention  1  0/264 (0.00%)  1/260 (0.38%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  3/264 (1.14%)  0/260 (0.00%) 
Acute respiratory failure  1  3/264 (1.14%)  1/260 (0.38%) 
Asthma  1  0/264 (0.00%)  1/260 (0.38%) 
Chronic obstructive pulmonary disease  1  2/264 (0.76%)  1/260 (0.38%) 
Dyspnoea  1  2/264 (0.76%)  2/260 (0.77%) 
Epistaxis  1  1/264 (0.38%)  0/260 (0.00%) 
Haemothorax  1  1/264 (0.38%)  0/260 (0.00%) 
Pleural effusion  1  1/264 (0.38%)  1/260 (0.38%) 
Pulmonary embolism  1  3/264 (1.14%)  1/260 (0.38%) 
Pulmonary hypertension  1  1/264 (0.38%)  0/260 (0.00%) 
Pulmonary oedema  1  3/264 (1.14%)  0/260 (0.00%) 
Respiratory failure  1  1/264 (0.38%)  1/260 (0.38%) 
Rhinitis allergic  1  1/264 (0.38%)  0/260 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin ulcer  1  0/264 (0.00%)  1/260 (0.38%) 
Vascular disorders     
Deep vein thrombosis  1  1/264 (0.38%)  1/260 (0.38%) 
Extremity necrosis  1  0/264 (0.00%)  1/260 (0.38%) 
Hypertensive crisis  1  2/264 (0.76%)  0/260 (0.00%) 
Hypertensive emergency  1  1/264 (0.38%)  0/260 (0.00%) 
Hypotension  1  5/264 (1.89%)  2/260 (0.77%) 
Hypovolaemic shock  1  1/264 (0.38%)  0/260 (0.00%) 
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 10 mg Empagliflozin
Affected / at Risk (%) Affected / at Risk (%)
Total   19/264 (7.20%)   20/260 (7.69%) 
Vascular disorders     
Hypotension  1  19/264 (7.20%)  20/260 (7.69%) 
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim
Organization: Boehringer Ingelheim, Call Centre
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT04157751    
Other Study ID Numbers: 1245-0204
2019-002946-19 ( EudraCT Number )
First Submitted: November 4, 2019
First Posted: November 8, 2019
Results First Submitted: May 10, 2022
Results First Posted: June 6, 2022
Last Update Posted: July 19, 2022