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EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced)

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ClinicalTrials.gov Identifier: NCT03057977
Recruitment Status : Completed
First Posted : February 20, 2017
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
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
Enrollment 3730
Recruitment Details A randomised, double-blind trial to demonstrate superiority of empagliflozin versus placebo, in patients with chronic Heart Failure with reduced Ejection Fraction (HFrEF).
Pre-assignment Details Patients were included in the trial after they had signed the informed consent form (ICF). All patients who met the all inclusion and none of the exclusion criteria during screening and at the randomisation approximately 1 to 4 weeks later were randomised to empagliflozin or placebo in a 1:1 ratio.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description 1 film-coated tablet of matching placebo was administered orally once daily. Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Period Title: Discontinuation From Treatment
Started [1] 1867 1863
Treated 1863 1863
Completed [2] 1352 1381
Not Completed 515 482
Reason Not Completed
Withdrawal by Subject             124             92
Lost to Follow-up             11             17
Protocol Violation             6             5
Not treated             4             0
Adverse Event             343             337
Reason Unknown             0             1
Personal Reasons             1             1
Unblinded medication             1             0
Patient received Empagliflozin for Diabetes             1             1
Principle Investigator Decision             2             0
Other medical condition (no Adverse Event)             2             4
Patient moved away/being abroad             4             3
Unable to continue treatment             4             1
Not attending study visit             3             10
Due to Covid-19 Pandemic             1             4
Patient decision to stop/interrupt medication             8             6
[1]
Randomized
[2]
Completed treatment
Period Title: Discontinuation From Trial
Started [1] 1867 1863
Treated 1863 1863
Completed 1847 1841
Not Completed 20 22
Reason Not Completed
Lost to follow-up to primary endpoint             9             9
Limited follow-up agreed             2             2
Withdrawal by Subject             9             11
[1]
Randomized
Arm/Group Title Placebo 10 mg Empagliflozin Total
Hide Arm/Group Description 1 film-coated tablet of matching placebo was administered orally once daily. Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. Total of all reporting groups
Overall Number of Baseline Participants 1867 1863 3730
Hide Baseline Analysis Population Description
Randomised Set (RS): All randomised patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1867 participants 1863 participants 3730 participants
66.5  (11.2) 67.2  (10.8) 66.8  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1867 participants 1863 participants 3730 participants
Female
456
  24.4%
437
  23.5%
893
  23.9%
Male
1411
  75.6%
1426
  76.5%
2837
  76.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1867 participants 1863 participants 3730 participants
Hispanic or Latino
613
  32.8%
616
  33.1%
1229
  32.9%
Not Hispanic or Latino
1178
  63.1%
1164
  62.5%
2342
  62.8%
Unknown or Not Reported
76
   4.1%
83
   4.5%
159
   4.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1867 participants 1863 participants 3730 participants
American Indian or Alaska Native
24
   1.3%
15
   0.8%
39
   1.0%
Asian
335
  17.9%
337
  18.1%
672
  18.0%
Native Hawaiian or Other Pacific Islander
6
   0.3%
8
   0.4%
14
   0.4%
Black or African American
134
   7.2%
123
   6.6%
257
   6.9%
White
1304
  69.8%
1325
  71.1%
2629
  70.5%
More than one race
33
   1.8%
28
   1.5%
61
   1.6%
Unknown or Not Reported
31
   1.7%
27
   1.4%
58
   1.6%
1.Primary Outcome
Title Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF)
Hide Description

Time to the first event of adjudicated cardiovascular (CV) death or adjudicated hospitalisation for heart failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25.

Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Time Frame From randomisation until completion of the planned treatment period, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set: All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events/ 100 pt-yrs at risk
21.00
(19.13 to 22.96)
15.77
(14.19 to 17.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 10 mg Empagliflozin
Comments

Model with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment.

alpha = 0.0496 (resulting from interim analysis) eGFR (CKP-EPI)cr: Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement LVEF: Left ventricular ejection fraction.

Type of Statistical Test Superiority
Comments H0: There is no difference between the effect of placebo and the effect of empagliflozin.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95.04%
0.65 to 0.86
Estimation Comments Comparison vs. Placebo [T/P]
2.Secondary Outcome
Title Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent)
Hide Description

Reported is the total number of HHF events (first and recurrent) which occurred.

All data up to the end of the planned treatment period (including the data after the end of treatment for patients not completing the treatment period as planned) from all randomised patients was used.

Time Frame From randomisation until completion of the planned treatment phase, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Unit of Measure: HHF events
553 388
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 10 mg Empagliflozin
Comments

Model accounts for dependence between recurrent HHF and cardiovascular death, with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment.

eGFR (CKP-EPI)cr: Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement LVEF: Left ventricular ejection fraction.

Type of Statistical Test Superiority
Comments H0: There is no difference between the effect of placebo and the effect of empagliflozin.
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Joint frailty model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95.04%
0.58 to 0.85
Estimation Comments HR vs placebo of recurrent HFF
3.Secondary Outcome
Title eGFR (CKD-EPI) cr Slope of Change From Baseline
Hide Description

Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) [mL/min/1.73m2] slope of change from baseline.

Available on-treatment change-from-baseline data were to be used. Patients without on-treatment data after randomisation were not to be included in this analysis. Slope represents the long term effect on eGFR.

Timepoints after baseline were included in calculation of slope of change from baseline. Descriptive statistic (mean(standard error)) is reported.

Time Frame Assessed at baseline, week 4, 12, 32, 52, 76, 100, 124, 148 and at end of treatment (EOT), up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set (TS): All patients treated with at least one dose of the study medication and at least one on-treatment measurement of eGFR.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1792 1799
Mean (Standard Error)
Unit of Measure: Milliliter/minute/1.73 meters squared
-2.278  (0.229) -0.546  (0.227)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 10 mg Empagliflozin
Comments

Random coefficient model allowing for random intercept and random slope per patient, with the same factors used for the primary endpoint (age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment) and additional factors "time", "treatment-by-time interaction", and "baseline eGFR (CKD-EPI)cr-by-time interaction". Only "on-treatment" data from treated patients were used.

alpha=0.001

Type of Statistical Test Superiority
Comments H0: There is no difference between the effect of placebo and the effect of empagliflozin.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Random intercept random coef. model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment by time interaction
Estimated Value 1.733
Confidence Interval (2-Sided) 99.9%
0.669 to 2.796
Estimation Comments Empa vs Placebo slope [/year]
4.Secondary Outcome
Title Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr
Hide Description

Time to the first event in the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), 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).

The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25.

Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Time Frame From randomisation until completion of the planned treatment period, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set: All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events/ 100 pt-yrs at risk
3.07
(2.33 to 3.91)
1.56
(1.06 to 2.17)
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 0.0019
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.32 to 0.77
Estimation Comments Comparison vs. Placebo
5.Secondary Outcome
Title Time to First Adjudicated Hospitalisation for Heart Failure (HHF)
Hide Description

Time to first adjudicated Hospitalisation for Heart Failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Time Frame From randomisation until completion of the planned treatment period, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events/ 100 pt-yrs at risk
15.55
(13.94 to 17.24)
10.75
(9.45 to 12.13)
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 <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.59 to 0.81
Estimation Comments Comparison vs Placebo
6.Secondary Outcome
Title Time to Adjudicated Cardiovascular (CV) Death
Hide Description

Time to adjudicated CV (Cardiovascular) death. The incidence rate (patients with events per 100 person years at risk) is reported.

The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25.

Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Time Frame From randomisation until completion of the planned treatment period, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set: All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events/ 100 pt-yrs at risk
8.13
(7.05 to 9.29)
7.55
(6.51 to 8.67)
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 0.4133
Comments [Not Specified]
Method Regression, Cox
Comments Model with terms for age, baseline eGFR (CKD-EPI), region, baseline diabetes status, sex, baseline LVEF and treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.75 to 1.12
Estimation Comments Comparison vs. Placebo
7.Secondary Outcome
Title Time to All-cause Mortality
Hide Description

Time to all-cause mortality. The incidence rate (patients with events per 100 person years at risk) is reported.

The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25.

Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Time Frame From randomisation until completion of the planned treatment period, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set: All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events/ 100 pt-yrs at risk
10.71
(9.46 to 12.04)
10.06
(8.85 to 11.34)
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 0.3536
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with terms for age, baseline eGFR (CKD-EPI), region, baseline diabetes status, sex, baseline LVEF and treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.77 to 1.10
Estimation Comments Comparison vs. placebo
8.Secondary Outcome
Title Time to Onset of Diabetes Mellitus (DM)
Hide Description

Time to onset of DM (Glycated haemoglobin (HbA1c) ≥6.5% or as diagnosed by the investigator) in patients with pre-DM (no history of DM and no HbA1c ≥6.5% before treatment, and a pre-treatment HbA1c value of 5.7 to <6.5%). The incidence rate (patients with events per 100 person years at risk) is reported.

The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25.

Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Time Frame From randomisation until completion of the planned treatment period, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the randomised set with pre-DM.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 636 632
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Patients with events/ 100 pt-yrs at risk
10.62
(8.42 to 13.07)
9.31
(7.27 to 11.60)
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 0.3576
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with terms for age, baseline eGFR (CDK-EPI), region, sex, baseline LVEF and treatment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.62 to 1.19
Estimation Comments Comparison vs. placebo
9.Secondary Outcome
Title Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52
Hide Description

Change from baseline in KCCQ (Kansas City cardiomyopathy questionnaire) clinical summary score at Week 52. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, selfefficacy, and quality of life in patients with Heart Failure. The KCCQ-clinical summary score comprises the following domains: Symptom frequency, symptom burden and physical limitation. The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status.

For patients who died, a worst score (score of 0) is imputed at all subsequent scheduled visits after the date of death.

Standard error is adjusted standard error. Change from baseline in KCCQ-score at week 52 was modeled using a MMRM with visit (week 12, 32 and 52) as repeated measures, adjusted mean (standard error) at week 52 is reported.

Time Frame Assessed at baseline, week 12, week 32 and week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the randomized set (RS) with available data for this endpoint, including values obtained on treatment or post-treatment.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1395 1401
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-3.36  (0.69) -1.30  (0.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 10 mg Empagliflozin
Comments Mixed model with age, baseline eGFR (CKD-EPI) as linear covariate(s) and region, baseline diabetes status, sex, baseline LVEF, week reachable, treatment by visit interaction, baseline KCCQ - Clinical Summary Score by Visit interaction as fixed effects. An unstructured covariance structure has been used.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0340
Comments [Not Specified]
Method Mixed Model
Comments Mixed model for repeated measures (MMRM)
Method of Estimation Estimation Parameter Difference of adjusted means
Estimated Value 2.06
Confidence Interval (2-Sided) 95%
0.16 to 3.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.97
Estimation Comments Comparison vs. placebo
10.Secondary Outcome
Title Number of All-cause Hospitalizations (First and Recurrent)
Hide Description Number of all-cause hospitalizations (first and recurrent).
Time Frame From randomisation until completion of the planned treatment phase, up to 1040 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set: All randomised patients.
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description:
1 film-coated tablet of matching placebo was administered orally once daily.
Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
Overall Number of Participants Analyzed 1867 1863
Measure Type: Number
Unit of Measure: Hospitalizations for any cause
1570 1364
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 10 mg Empagliflozin
Comments Joint frailty model with terms for age, baseline eGFR (CDK-EPI), region, sex, baseline diabetes status and baseline LVEF. Model accounts for dependence between recurrent all-cause hospitalizations and all-cause mortality.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method Joint frailty model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.75 to 0.95
Estimation Comments Comparison vs. placebo
Time Frame From first intake of study medication until end of planned treatment period + 7 days (Residual Effect Period), up to 1047 days.
Adverse Event Reporting Description [All-Cause Mortality]: Randomised Set: All randomised patients. [Serious Adverse Events and Other Adverse Events]: Treated Set: All patients treated with at least one dose of study drug.
 
Arm/Group Title Placebo 10 mg Empagliflozin
Hide Arm/Group Description 1 film-coated tablet of matching placebo was administered orally once daily. Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily.
All-Cause Mortality
Placebo 10 mg Empagliflozin
Affected / at Risk (%) Affected / at Risk (%)
Total   266/1867 (14.25%)   249/1863 (13.37%) 
Hide Serious Adverse Events
Placebo 10 mg Empagliflozin
Affected / at Risk (%) Affected / at Risk (%)
Total   896/1863 (48.09%)   772/1863 (41.44%) 
Blood and lymphatic system disorders     
Anaemia  1  6/1863 (0.32%)  10/1863 (0.54%) 
Blood loss anaemia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Disseminated intravascular coagulation  1  0/1863 (0.00%)  1/1863 (0.05%) 
Iron deficiency anaemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Leukocytosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pancytopenia  1  1/1863 (0.05%)  1/1863 (0.05%) 
Splenic haematoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Splenic infarction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Thrombocytopenia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cardiac disorders     
Acute coronary syndrome  1  3/1863 (0.16%)  0/1863 (0.00%) 
Acute left ventricular failure  1  5/1863 (0.27%)  7/1863 (0.38%) 
Acute myocardial infarction  1  18/1863 (0.97%)  24/1863 (1.29%) 
Angina pectoris  1  10/1863 (0.54%)  6/1863 (0.32%) 
Angina unstable  1  9/1863 (0.48%)  11/1863 (0.59%) 
Aortic valve stenosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Arrhythmia  1  1/1863 (0.05%)  1/1863 (0.05%) 
Arrhythmia supraventricular  1  0/1863 (0.00%)  1/1863 (0.05%) 
Arteriosclerosis coronary artery  1  2/1863 (0.11%)  0/1863 (0.00%) 
Atrial fibrillation  1  44/1863 (2.36%)  24/1863 (1.29%) 
Atrial flutter  1  11/1863 (0.59%)  3/1863 (0.16%) 
Atrial tachycardia  1  2/1863 (0.11%)  4/1863 (0.21%) 
Atrial thrombosis  1  2/1863 (0.11%)  2/1863 (0.11%) 
Atrioventricular block complete  1  1/1863 (0.05%)  4/1863 (0.21%) 
Atrioventricular block second degree  1  0/1863 (0.00%)  1/1863 (0.05%) 
Bradyarrhythmia  1  0/1863 (0.00%)  2/1863 (0.11%) 
Bradycardia  1  4/1863 (0.21%)  0/1863 (0.00%) 
Bundle branch block left  1  1/1863 (0.05%)  1/1863 (0.05%) 
Cardiac aneurysm  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cardiac arrest  1  10/1863 (0.54%)  9/1863 (0.48%) 
Cardiac asthma  1  0/1863 (0.00%)  2/1863 (0.11%) 
Cardiac disorder  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cardiac dysfunction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cardiac failure  1  444/1863 (23.83%)  332/1863 (17.82%) 
Cardiac failure acute  1  29/1863 (1.56%)  19/1863 (1.02%) 
Cardiac failure chronic  1  32/1863 (1.72%)  18/1863 (0.97%) 
Cardiac failure congestive  1  41/1863 (2.20%)  26/1863 (1.40%) 
Cardiac tamponade  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cardiac ventricular thrombosis  1  2/1863 (0.11%)  5/1863 (0.27%) 
Cardio-respiratory arrest  1  4/1863 (0.21%)  1/1863 (0.05%) 
Cardiogenic shock  1  11/1863 (0.59%)  8/1863 (0.43%) 
Cardiomegaly  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cardiomyopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cardiopulmonary failure  1  1/1863 (0.05%)  1/1863 (0.05%) 
Cardiorenal syndrome  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cardiovascular disorder  1  0/1863 (0.00%)  1/1863 (0.05%) 
Chronic left ventricular failure  1  0/1863 (0.00%)  1/1863 (0.05%) 
Congestive cardiomyopathy  1  6/1863 (0.32%)  1/1863 (0.05%) 
Coronary artery disease  1  16/1863 (0.86%)  2/1863 (0.11%) 
Coronary artery occlusion  1  3/1863 (0.16%)  3/1863 (0.16%) 
Coronary artery stenosis  1  2/1863 (0.11%)  3/1863 (0.16%) 
Coronary ostial stenosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Intracardiac thrombus  1  2/1863 (0.11%)  2/1863 (0.11%) 
Ischaemic cardiomyopathy  1  1/1863 (0.05%)  1/1863 (0.05%) 
Left ventricular dysfunction  1  1/1863 (0.05%)  1/1863 (0.05%) 
Left ventricular failure  1  3/1863 (0.16%)  3/1863 (0.16%) 
Low cardiac output syndrome  1  1/1863 (0.05%)  2/1863 (0.11%) 
Mitral valve incompetence  1  5/1863 (0.27%)  4/1863 (0.21%) 
Myocardial infarction  1  16/1863 (0.86%)  16/1863 (0.86%) 
Myocardial ischaemia  1  1/1863 (0.05%)  3/1863 (0.16%) 
Palpitations  1  1/1863 (0.05%)  0/1863 (0.00%) 
Paroxysmal atrioventricular block  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pericardial effusion  1  0/1863 (0.00%)  1/1863 (0.05%) 
Prinzmetal angina  1  1/1863 (0.05%)  1/1863 (0.05%) 
Pulseless electrical activity  1  1/1863 (0.05%)  0/1863 (0.00%) 
Right ventricular failure  1  1/1863 (0.05%)  1/1863 (0.05%) 
Supraventricular tachycardia  1  6/1863 (0.32%)  2/1863 (0.11%) 
Torsade de pointes  1  0/1863 (0.00%)  1/1863 (0.05%) 
Trifascicular block  1  1/1863 (0.05%)  0/1863 (0.00%) 
Ventricular arrhythmia  1  5/1863 (0.27%)  1/1863 (0.05%) 
Ventricular extrasystoles  1  2/1863 (0.11%)  2/1863 (0.11%) 
Ventricular fibrillation  1  8/1863 (0.43%)  10/1863 (0.54%) 
Ventricular flutter  1  1/1863 (0.05%)  1/1863 (0.05%) 
Ventricular tachyarrhythmia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Ventricular tachycardia  1  37/1863 (1.99%)  55/1863 (2.95%) 
Congenital, familial and genetic disorders     
Dermoid cyst  1  2/1863 (0.11%)  0/1863 (0.00%) 
Gastrointestinal arteriovenous malformation  1  0/1863 (0.00%)  1/1863 (0.05%) 
Phimosis  1  1/1863 (0.05%)  1/1863 (0.05%) 
Type IV hyperlipidaemia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Ear and labyrinth disorders     
Deafness  1  1/1863 (0.05%)  0/1863 (0.00%) 
Deafness neurosensory  1  1/1863 (0.05%)  0/1863 (0.00%) 
Deafness unilateral  1  0/1863 (0.00%)  1/1863 (0.05%) 
Mixed deafness  1  0/1863 (0.00%)  1/1863 (0.05%) 
Sudden hearing loss  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vertigo  1  0/1863 (0.00%)  1/1863 (0.05%) 
Vertigo positional  1  0/1863 (0.00%)  1/1863 (0.05%) 
Endocrine disorders     
Cushing's syndrome  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hyperthyroidism  1  2/1863 (0.11%)  3/1863 (0.16%) 
Hypothyroidism  1  2/1863 (0.11%)  0/1863 (0.00%) 
Eye disorders     
Cataract  1  3/1863 (0.16%)  5/1863 (0.27%) 
Cataract cortical  1  0/1863 (0.00%)  1/1863 (0.05%) 
Diabetic retinopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Glaucoma  1  5/1863 (0.27%)  3/1863 (0.16%) 
Macular degeneration  1  1/1863 (0.05%)  0/1863 (0.00%) 
Open angle glaucoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Retinal detachment  1  0/1863 (0.00%)  3/1863 (0.16%) 
Retinal tear  1  1/1863 (0.05%)  1/1863 (0.05%) 
Vitreous haemorrhage  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  3/1863 (0.16%)  3/1863 (0.16%) 
Abdominal pain upper  1  0/1863 (0.00%)  2/1863 (0.11%) 
Abdominal wall haematoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Acute abdomen  1  1/1863 (0.05%)  1/1863 (0.05%) 
Chronic gastritis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Coeliac disease  1  0/1863 (0.00%)  1/1863 (0.05%) 
Colitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Colitis ischaemic  1  1/1863 (0.05%)  1/1863 (0.05%) 
Constipation  1  1/1863 (0.05%)  3/1863 (0.16%) 
Diarrhoea  1  2/1863 (0.11%)  2/1863 (0.11%) 
Duodenal ulcer  1  0/1863 (0.00%)  2/1863 (0.11%) 
Enteritis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Erosive oesophagitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Gastric haemorrhage  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gastric mucosa erythema  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gastric perforation  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gastric ulcer  1  0/1863 (0.00%)  1/1863 (0.05%) 
Gastritis  1  1/1863 (0.05%)  2/1863 (0.11%) 
Gastritis erosive  1  1/1863 (0.05%)  1/1863 (0.05%) 
Gastrointestinal haemorrhage  1  4/1863 (0.21%)  8/1863 (0.43%) 
Gastrointestinal necrosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gastrointestinal ulcer haemorrhage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Gastrointestinal vascular malformation haemorrhagic  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gingival bleeding  1  1/1863 (0.05%)  0/1863 (0.00%) 
Haematochezia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Haemorrhoids  1  0/1863 (0.00%)  2/1863 (0.11%) 
Ileus  1  0/1863 (0.00%)  1/1863 (0.05%) 
Ileus paralytic  1  1/1863 (0.05%)  0/1863 (0.00%) 
Incarcerated inguinal hernia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Inguinal hernia  1  0/1863 (0.00%)  7/1863 (0.38%) 
Intestinal ischaemia  1  2/1863 (0.11%)  0/1863 (0.00%) 
Intestinal obstruction  1  2/1863 (0.11%)  2/1863 (0.11%) 
Intussusception  1  1/1863 (0.05%)  0/1863 (0.00%) 
Large intestine polyp  1  2/1863 (0.11%)  1/1863 (0.05%) 
Mallory-Weiss syndrome  1  0/1863 (0.00%)  1/1863 (0.05%) 
Mechanical ileus  1  0/1863 (0.00%)  1/1863 (0.05%) 
Mesenteric artery stenosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Nausea  1  1/1863 (0.05%)  1/1863 (0.05%) 
Obstructive pancreatitis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Oesophageal obstruction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pancreatitis  1  1/1863 (0.05%)  1/1863 (0.05%) 
Pancreatitis acute  1  2/1863 (0.11%)  1/1863 (0.05%) 
Pancreatitis chronic  1  1/1863 (0.05%)  0/1863 (0.00%) 
Periodontal disease  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pharyngo-oesophageal diverticulum  1  0/1863 (0.00%)  1/1863 (0.05%) 
Rectal haemorrhage  1  3/1863 (0.16%)  3/1863 (0.16%) 
Small intestinal obstruction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Upper gastrointestinal haemorrhage  1  7/1863 (0.38%)  5/1863 (0.27%) 
Vomiting  1  1/1863 (0.05%)  0/1863 (0.00%) 
General disorders     
Cardiac death  1  8/1863 (0.43%)  4/1863 (0.21%) 
Chest pain  1  2/1863 (0.11%)  2/1863 (0.11%) 
Death  1  27/1863 (1.45%)  20/1863 (1.07%) 
Discomfort  1  1/1863 (0.05%)  0/1863 (0.00%) 
Euthanasia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Foreign body reaction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gait disturbance  1  0/1863 (0.00%)  1/1863 (0.05%) 
Implant site haematoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Medical device site haematoma  1  2/1863 (0.11%)  0/1863 (0.00%) 
Multiple organ dysfunction syndrome  1  1/1863 (0.05%)  1/1863 (0.05%) 
Non-cardiac chest pain  1  7/1863 (0.38%)  5/1863 (0.27%) 
Oedema due to cardiac disease  1  0/1863 (0.00%)  1/1863 (0.05%) 
Oedema peripheral  1  2/1863 (0.11%)  3/1863 (0.16%) 
Pyrexia  1  1/1863 (0.05%)  1/1863 (0.05%) 
Stent-graft endoleak  1  2/1863 (0.11%)  0/1863 (0.00%) 
Sudden cardiac death  1  10/1863 (0.54%)  8/1863 (0.43%) 
Sudden death  1  5/1863 (0.27%)  5/1863 (0.27%) 
Systemic inflammatory response syndrome  1  0/1863 (0.00%)  1/1863 (0.05%) 
Vascular device occlusion  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vessel puncture site phlebitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hepatobiliary disorders     
Acute hepatic failure  1  0/1863 (0.00%)  1/1863 (0.05%) 
Bile duct obstruction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Bile duct stone  1  1/1863 (0.05%)  1/1863 (0.05%) 
Cardiac cirrhosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cholangitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cholangitis acute  1  1/1863 (0.05%)  1/1863 (0.05%) 
Cholecystitis  1  3/1863 (0.16%)  2/1863 (0.11%) 
Cholecystitis acute  1  5/1863 (0.27%)  2/1863 (0.11%) 
Cholecystitis chronic  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cholelithiasis  1  2/1863 (0.11%)  1/1863 (0.05%) 
Drug-induced liver injury  1  1/1863 (0.05%)  1/1863 (0.05%) 
Hepatic cirrhosis  1  1/1863 (0.05%)  1/1863 (0.05%) 
Hepatic failure  1  2/1863 (0.11%)  1/1863 (0.05%) 
Hepatic function abnormal  1  4/1863 (0.21%)  1/1863 (0.05%) 
Hepatic steatosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hepatitis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Liver disorder  1  0/1863 (0.00%)  1/1863 (0.05%) 
Liver injury  1  5/1863 (0.27%)  3/1863 (0.16%) 
Non-alcoholic steatohepatitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Immune system disorders     
Heart transplant rejection  1  1/1863 (0.05%)  0/1863 (0.00%) 
Infections and infestations     
Abdominal sepsis  1  0/1863 (0.00%)  2/1863 (0.11%) 
Appendicitis  1  3/1863 (0.16%)  3/1863 (0.16%) 
Appendicitis perforated  1  0/1863 (0.00%)  2/1863 (0.11%) 
Atypical pneumonia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Bacteraemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Bacterial sepsis  1  0/1863 (0.00%)  2/1863 (0.11%) 
Bronchitis  1  5/1863 (0.27%)  5/1863 (0.27%) 
Bullous erysipelas  1  1/1863 (0.05%)  0/1863 (0.00%) 
COVID-19  1  3/1863 (0.16%)  1/1863 (0.05%) 
COVID-19 pneumonia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cellulitis  1  3/1863 (0.16%)  8/1863 (0.43%) 
Clostridium difficile infection  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cystitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Dengue fever  1  1/1863 (0.05%)  0/1863 (0.00%) 
Device related infection  1  0/1863 (0.00%)  2/1863 (0.11%) 
Diabetic foot infection  1  0/1863 (0.00%)  3/1863 (0.16%) 
Disseminated tuberculosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Diverticulitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Encephalitis viral  1  1/1863 (0.05%)  0/1863 (0.00%) 
Endocarditis  1  3/1863 (0.16%)  2/1863 (0.11%) 
Erysipelas  1  3/1863 (0.16%)  1/1863 (0.05%) 
Escherichia bacteraemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Eye abscess  1  1/1863 (0.05%)  0/1863 (0.00%) 
Fournier's gangrene  1  0/1863 (0.00%)  1/1863 (0.05%) 
Gangrene  1  1/1863 (0.05%)  4/1863 (0.21%) 
Gastritis viral  1  0/1863 (0.00%)  1/1863 (0.05%) 
Gastroenteritis  1  9/1863 (0.48%)  4/1863 (0.21%) 
Gastrointestinal infection  1  2/1863 (0.11%)  1/1863 (0.05%) 
Haemorrhagic fever  1  1/1863 (0.05%)  0/1863 (0.00%) 
Herpes zoster  1  2/1863 (0.11%)  0/1863 (0.00%) 
Human anaplasmosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Implant site infection  1  0/1863 (0.00%)  1/1863 (0.05%) 
Infected skin ulcer  1  0/1863 (0.00%)  1/1863 (0.05%) 
Infection  1  2/1863 (0.11%)  0/1863 (0.00%) 
Infective spondylitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Influenza  1  5/1863 (0.27%)  4/1863 (0.21%) 
Intervertebral discitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Labyrinthitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Localised infection  1  2/1863 (0.11%)  0/1863 (0.00%) 
Lower respiratory tract infection  1  2/1863 (0.11%)  2/1863 (0.11%) 
Medical device site infection  1  0/1863 (0.00%)  1/1863 (0.05%) 
Nail infection  1  1/1863 (0.05%)  0/1863 (0.00%) 
Nocardiosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Osteomyelitis  1  2/1863 (0.11%)  2/1863 (0.11%) 
Osteomyelitis chronic  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pelvic abscess  1  1/1863 (0.05%)  0/1863 (0.00%) 
Perineal abscess  1  1/1863 (0.05%)  0/1863 (0.00%) 
Peritonitis  1  1/1863 (0.05%)  2/1863 (0.11%) 
Peritonitis bacterial  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pharyngitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pneumonia  1  62/1863 (3.33%)  53/1863 (2.84%) 
Pneumonia bacterial  1  3/1863 (0.16%)  1/1863 (0.05%) 
Pneumonia chlamydial  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pneumonia influenzal  1  0/1863 (0.00%)  1/1863 (0.05%) 
Postoperative wound infection  1  2/1863 (0.11%)  0/1863 (0.00%) 
Pulmonary sepsis  1  0/1863 (0.00%)  2/1863 (0.11%) 
Pulmonary tuberculosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pyelitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pyelonephritis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pyelonephritis acute  1  2/1863 (0.11%)  0/1863 (0.00%) 
Respiratory syncytial virus bronchitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Respiratory tract infection  1  0/1863 (0.00%)  1/1863 (0.05%) 
Sepsis  1  8/1863 (0.43%)  8/1863 (0.43%) 
Septic encephalopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Septic shock  1  5/1863 (0.27%)  9/1863 (0.48%) 
Sinobronchitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Spinal cord abscess  1  0/1863 (0.00%)  2/1863 (0.11%) 
Staphylococcal bacteraemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Staphylococcal sepsis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Streptococcal sepsis  1  1/1863 (0.05%)  1/1863 (0.05%) 
Upper respiratory tract infection  1  1/1863 (0.05%)  2/1863 (0.11%) 
Urinary tract infection  1  10/1863 (0.54%)  14/1863 (0.75%) 
Urosepsis  1  0/1863 (0.00%)  4/1863 (0.21%) 
Vessel puncture site cellulitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Viral diarrhoea  1  1/1863 (0.05%)  0/1863 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  3/1863 (0.16%)  2/1863 (0.11%) 
Avulsion fracture  1  0/1863 (0.00%)  2/1863 (0.11%) 
Bladder injury  1  0/1863 (0.00%)  1/1863 (0.05%) 
Carbon monoxide poisoning  1  1/1863 (0.05%)  0/1863 (0.00%) 
Concussion  1  1/1863 (0.05%)  0/1863 (0.00%) 
Contusion  1  1/1863 (0.05%)  1/1863 (0.05%) 
Coronary artery restenosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Costal cartilage fracture  1  0/1863 (0.00%)  1/1863 (0.05%) 
Craniocerebral injury  1  1/1863 (0.05%)  1/1863 (0.05%) 
Fall  1  4/1863 (0.21%)  15/1863 (0.81%) 
Femoral neck fracture  1  2/1863 (0.11%)  1/1863 (0.05%) 
Femur fracture  1  3/1863 (0.16%)  5/1863 (0.27%) 
Fibula fracture  1  1/1863 (0.05%)  0/1863 (0.00%) 
Fracture  1  0/1863 (0.00%)  1/1863 (0.05%) 
Head injury  1  0/1863 (0.00%)  3/1863 (0.16%) 
Heat stroke  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hip fracture  1  3/1863 (0.16%)  2/1863 (0.11%) 
Humerus fracture  1  1/1863 (0.05%)  2/1863 (0.11%) 
Jaw fracture  1  0/1863 (0.00%)  1/1863 (0.05%) 
Joint dislocation  1  1/1863 (0.05%)  0/1863 (0.00%) 
Limb crushing injury  1  0/1863 (0.00%)  1/1863 (0.05%) 
Limb injury  1  1/1863 (0.05%)  1/1863 (0.05%) 
Lumbar vertebral fracture  1  1/1863 (0.05%)  2/1863 (0.11%) 
Multiple injuries  1  2/1863 (0.11%)  0/1863 (0.00%) 
Open globe injury  1  1/1863 (0.05%)  0/1863 (0.00%) 
Overdose  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pelvic fracture  1  3/1863 (0.16%)  1/1863 (0.05%) 
Post procedural haemorrhage  1  1/1863 (0.05%)  0/1863 (0.00%) 
Post procedural swelling  1  1/1863 (0.05%)  0/1863 (0.00%) 
Post-traumatic pain  1  1/1863 (0.05%)  0/1863 (0.00%) 
Postoperative respiratory failure  1  0/1863 (0.00%)  1/1863 (0.05%) 
Procedural shock  1  0/1863 (0.00%)  2/1863 (0.11%) 
Rib fracture  1  2/1863 (0.11%)  0/1863 (0.00%) 
Road traffic accident  1  2/1863 (0.11%)  4/1863 (0.21%) 
Skin laceration  1  0/1863 (0.00%)  2/1863 (0.11%) 
Spinal compression fracture  1  0/1863 (0.00%)  1/1863 (0.05%) 
Splenic rupture  1  0/1863 (0.00%)  1/1863 (0.05%) 
Subdural haematoma  1  0/1863 (0.00%)  2/1863 (0.11%) 
Subdural haemorrhage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Thermal burn  1  0/1863 (0.00%)  1/1863 (0.05%) 
Tibia fracture  1  1/1863 (0.05%)  0/1863 (0.00%) 
Tooth fracture  1  1/1863 (0.05%)  0/1863 (0.00%) 
Toxicity to various agents  1  1/1863 (0.05%)  0/1863 (0.00%) 
Traumatic fracture  1  0/1863 (0.00%)  6/1863 (0.32%) 
Traumatic haematoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Traumatic intracranial haemorrhage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Upper limb fracture  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vascular pseudoaneurysm  1  2/1863 (0.11%)  1/1863 (0.05%) 
Wound dehiscence  1  1/1863 (0.05%)  1/1863 (0.05%) 
Wrist fracture  1  1/1863 (0.05%)  0/1863 (0.00%) 
Investigations     
Aspartate aminotransferase increased  1  0/1863 (0.00%)  1/1863 (0.05%) 
Blood creatinine increased  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cardiac electrophysiologic study  1  1/1863 (0.05%)  0/1863 (0.00%) 
Ejection fraction decreased  1  1/1863 (0.05%)  0/1863 (0.00%) 
Endoscopic retrograde cholangiopancreatography  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hepatic enzyme abnormal  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hepatic enzyme increased  1  1/1863 (0.05%)  0/1863 (0.00%) 
Weight increased  1  1/1863 (0.05%)  0/1863 (0.00%) 
Metabolism and nutrition disorders     
Acidosis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Cachexia  1  1/1863 (0.05%)  1/1863 (0.05%) 
Decreased appetite  1  1/1863 (0.05%)  0/1863 (0.00%) 
Dehydration  1  4/1863 (0.21%)  8/1863 (0.43%) 
Diabetes mellitus  1  5/1863 (0.27%)  4/1863 (0.21%) 
Diabetes mellitus inadequate control  1  2/1863 (0.11%)  0/1863 (0.00%) 
Diabetic complication  1  1/1863 (0.05%)  0/1863 (0.00%) 
Diabetic metabolic decompensation  1  7/1863 (0.38%)  2/1863 (0.11%) 
Gout  1  3/1863 (0.16%)  1/1863 (0.05%) 
Hyperglycaemia  1  2/1863 (0.11%)  0/1863 (0.00%) 
Hyperglycaemic hyperosmolar nonketotic syndrome  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hyperkalaemia  1  9/1863 (0.48%)  2/1863 (0.11%) 
Hypernatraemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hypoglycaemia  1  5/1863 (0.27%)  6/1863 (0.32%) 
Hypokalaemia  1  2/1863 (0.11%)  3/1863 (0.16%) 
Hyponatraemia  1  2/1863 (0.11%)  1/1863 (0.05%) 
Hypophagia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hypovolaemia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Lactic acidosis  1  0/1863 (0.00%)  2/1863 (0.11%) 
Metabolic acidosis  1  3/1863 (0.16%)  4/1863 (0.21%) 
Type 2 diabetes mellitus  1  0/1863 (0.00%)  1/1863 (0.05%) 
Musculoskeletal and connective tissue disorders     
Ankylosing spondylitis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Arthralgia  1  1/1863 (0.05%)  1/1863 (0.05%) 
Arthropathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Back pain  1  1/1863 (0.05%)  2/1863 (0.11%) 
Cervical spinal stenosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Crystal arthropathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Gouty arthritis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Intervertebral disc disorder  1  0/1863 (0.00%)  1/1863 (0.05%) 
Joint destruction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Lumbar spinal stenosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Muscular weakness  1  1/1863 (0.05%)  1/1863 (0.05%) 
Musculoskeletal chest pain  1  1/1863 (0.05%)  2/1863 (0.11%) 
Osteoarthritis  1  7/1863 (0.38%)  3/1863 (0.16%) 
Osteochondrosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pathological fracture  1  1/1863 (0.05%)  0/1863 (0.00%) 
Polymyalgia rheumatica  1  1/1863 (0.05%)  0/1863 (0.00%) 
Rhabdomyolysis  1  2/1863 (0.11%)  2/1863 (0.11%) 
Rotator cuff syndrome  1  1/1863 (0.05%)  1/1863 (0.05%) 
Spondylitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Systemic lupus erythematosus  1  1/1863 (0.05%)  0/1863 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Abdominal neoplasm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Adenocarcinoma gastric  1  1/1863 (0.05%)  0/1863 (0.00%) 
Adenocarcinoma of colon  1  2/1863 (0.11%)  2/1863 (0.11%) 
Adenocarcinoma of the cervix  1  0/1863 (0.00%)  1/1863 (0.05%) 
Adenocarcinoma pancreas  1  2/1863 (0.11%)  0/1863 (0.00%) 
Adrenal adenoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Basal cell carcinoma  1  4/1863 (0.21%)  4/1863 (0.21%) 
Bile duct adenocarcinoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Bladder cancer  1  3/1863 (0.16%)  1/1863 (0.05%) 
Bladder cancer stage IV  1  1/1863 (0.05%)  0/1863 (0.00%) 
Bladder neoplasm  1  1/1863 (0.05%)  1/1863 (0.05%) 
Bladder transitional cell carcinoma  1  1/1863 (0.05%)  1/1863 (0.05%) 
Bowen's disease  1  1/1863 (0.05%)  0/1863 (0.00%) 
Chronic lymphocytic leukaemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Chronic myelomonocytic leukaemia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Clear cell renal cell carcinoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Colon adenoma  1  1/1863 (0.05%)  1/1863 (0.05%) 
Colon cancer  1  3/1863 (0.16%)  0/1863 (0.00%) 
Cutaneous T-cell lymphoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Diffuse large B-cell lymphoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Diffuse large B-cell lymphoma recurrent  1  0/1863 (0.00%)  1/1863 (0.05%) 
Gastric cancer  1  2/1863 (0.11%)  0/1863 (0.00%) 
Gastrointestinal neoplasm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hepatic cancer  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hypergammaglobulinaemia benign monoclonal  1  1/1863 (0.05%)  0/1863 (0.00%) 
Invasive ductal breast carcinoma  1  1/1863 (0.05%)  1/1863 (0.05%) 
Lung neoplasm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Lung neoplasm malignant  1  2/1863 (0.11%)  0/1863 (0.00%) 
Malignant melanoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Metastases to spine  1  0/1863 (0.00%)  1/1863 (0.05%) 
Metastatic carcinoma of the bladder  1  1/1863 (0.05%)  0/1863 (0.00%) 
Metastatic neoplasm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Myelodysplastic syndrome  1  2/1863 (0.11%)  0/1863 (0.00%) 
Non-Hodgkin's lymphoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Oesophageal carcinoma  1  2/1863 (0.11%)  0/1863 (0.00%) 
Ovarian adenoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pancreatic carcinoma  1  3/1863 (0.16%)  0/1863 (0.00%) 
Pancreatic carcinoma metastatic  1  0/1863 (0.00%)  1/1863 (0.05%) 
Plasma cell myeloma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Prostate cancer  1  7/1863 (0.38%)  6/1863 (0.32%) 
Prostate cancer metastatic  1  0/1863 (0.00%)  1/1863 (0.05%) 
Rectal adenocarcinoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Renal cancer  1  0/1863 (0.00%)  1/1863 (0.05%) 
Renal cancer metastatic  1  0/1863 (0.00%)  1/1863 (0.05%) 
Renal neoplasm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Squamous cell carcinoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Squamous cell carcinoma of lung  1  2/1863 (0.11%)  0/1863 (0.00%) 
Squamous cell carcinoma of skin  1  1/1863 (0.05%)  6/1863 (0.32%) 
Transitional cell carcinoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Ureteric cancer  1  0/1863 (0.00%)  1/1863 (0.05%) 
Nervous system disorders     
Brain injury  1  0/1863 (0.00%)  1/1863 (0.05%) 
Carotid arteriosclerosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Carotid artery occlusion  1  1/1863 (0.05%)  1/1863 (0.05%) 
Carotid artery stenosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cerebellar haemorrhage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cerebellar infarction  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cerebellar stroke  1  1/1863 (0.05%)  0/1863 (0.00%) 
Cerebral haematoma  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cerebral haemorrhage  1  1/1863 (0.05%)  2/1863 (0.11%) 
Cerebral hypoperfusion  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cerebral infarction  1  2/1863 (0.11%)  4/1863 (0.21%) 
Cerebral ischaemia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cerebrovascular accident  1  12/1863 (0.64%)  17/1863 (0.91%) 
Cerebrovascular insufficiency  1  0/1863 (0.00%)  1/1863 (0.05%) 
Dementia  1  3/1863 (0.16%)  0/1863 (0.00%) 
Dizziness  1  0/1863 (0.00%)  1/1863 (0.05%) 
Dysarthria  1  0/1863 (0.00%)  1/1863 (0.05%) 
Embolic stroke  1  0/1863 (0.00%)  1/1863 (0.05%) 
Epilepsy  1  3/1863 (0.16%)  2/1863 (0.11%) 
Guillain-Barre syndrome  1  1/1863 (0.05%)  0/1863 (0.00%) 
Haemorrhagic stroke  1  1/1863 (0.05%)  2/1863 (0.11%) 
Headache  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hemiparesis  1  1/1863 (0.05%)  1/1863 (0.05%) 
Hemiplegia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hepatic encephalopathy  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hyperglycaemic seizure  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hypoxic-ischaemic encephalopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Intracranial aneurysm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Ischaemic stroke  1  20/1863 (1.07%)  19/1863 (1.02%) 
Lacunar infarction  1  0/1863 (0.00%)  1/1863 (0.05%) 
Loss of consciousness  1  0/1863 (0.00%)  2/1863 (0.11%) 
Lumbar radiculopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Lumbosacral radiculopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Migraine  1  0/1863 (0.00%)  1/1863 (0.05%) 
Myoclonus  1  1/1863 (0.05%)  0/1863 (0.00%) 
Paraplegia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Peroneal nerve palsy  1  1/1863 (0.05%)  1/1863 (0.05%) 
Postresuscitation encephalopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Presyncope  1  0/1863 (0.00%)  4/1863 (0.21%) 
Seizure  1  3/1863 (0.16%)  2/1863 (0.11%) 
Spinal cord compression  1  0/1863 (0.00%)  1/1863 (0.05%) 
Subarachnoid haemorrhage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Syncope  1  8/1863 (0.43%)  17/1863 (0.91%) 
Transient ischaemic attack  1  9/1863 (0.48%)  5/1863 (0.27%) 
Uraemic encephalopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vascular dementia  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vascular encephalopathy  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vertebrobasilar insufficiency  1  1/1863 (0.05%)  0/1863 (0.00%) 
Product Issues     
Device breakage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Device dislocation  1  0/1863 (0.00%)  1/1863 (0.05%) 
Device failure  1  0/1863 (0.00%)  1/1863 (0.05%) 
Device inappropriate shock delivery  1  0/1863 (0.00%)  1/1863 (0.05%) 
Device lead damage  1  1/1863 (0.05%)  0/1863 (0.00%) 
Device lead issue  1  0/1863 (0.00%)  2/1863 (0.11%) 
Device malfunction  1  4/1863 (0.21%)  3/1863 (0.16%) 
Device physical property issue  1  1/1863 (0.05%)  0/1863 (0.00%) 
Psychiatric disorders     
Anxiety  1  1/1863 (0.05%)  0/1863 (0.00%) 
Bipolar disorder  1  0/1863 (0.00%)  1/1863 (0.05%) 
Completed suicide  1  0/1863 (0.00%)  1/1863 (0.05%) 
Delirium  1  4/1863 (0.21%)  8/1863 (0.43%) 
Delirium tremens  1  1/1863 (0.05%)  0/1863 (0.00%) 
Depression  1  1/1863 (0.05%)  0/1863 (0.00%) 
Drug abuse  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hallucination  1  0/1863 (0.00%)  1/1863 (0.05%) 
Renal and urinary disorders     
Acute kidney injury  1  55/1863 (2.95%)  35/1863 (1.88%) 
Azotaemia  1  2/1863 (0.11%)  0/1863 (0.00%) 
Chronic kidney disease  1  6/1863 (0.32%)  3/1863 (0.16%) 
Diabetic nephropathy  1  0/1863 (0.00%)  1/1863 (0.05%) 
Dysuria  1  1/1863 (0.05%)  1/1863 (0.05%) 
End stage renal disease  1  1/1863 (0.05%)  0/1863 (0.00%) 
Haematuria  1  2/1863 (0.11%)  1/1863 (0.05%) 
Hydronephrosis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Nephrolithiasis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Nephropathy  1  1/1863 (0.05%)  2/1863 (0.11%) 
Nephropathy toxic  1  1/1863 (0.05%)  0/1863 (0.00%) 
Prerenal failure  1  0/1863 (0.00%)  1/1863 (0.05%) 
Renal failure  1  14/1863 (0.75%)  9/1863 (0.48%) 
Renal impairment  1  27/1863 (1.45%)  17/1863 (0.91%) 
Renal infarct  1  1/1863 (0.05%)  0/1863 (0.00%) 
Renal tubular necrosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Ureterolithiasis  1  0/1863 (0.00%)  3/1863 (0.16%) 
Urethral stenosis  1  0/1863 (0.00%)  2/1863 (0.11%) 
Urinary retention  1  1/1863 (0.05%)  1/1863 (0.05%) 
Reproductive system and breast disorders     
Acquired hydrocele  1  1/1863 (0.05%)  0/1863 (0.00%) 
Balanoposthitis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Benign prostatic hyperplasia  1  1/1863 (0.05%)  1/1863 (0.05%) 
Fibrocystic breast disease  1  0/1863 (0.00%)  1/1863 (0.05%) 
Uterovaginal prolapse  1  0/1863 (0.00%)  1/1863 (0.05%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  2/1863 (0.11%)  3/1863 (0.16%) 
Acute respiratory failure  1  5/1863 (0.27%)  3/1863 (0.16%) 
Aspiration  1  1/1863 (0.05%)  0/1863 (0.00%) 
Asthma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Asthmatic crisis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Bronchiectasis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Bronchitis chronic  1  1/1863 (0.05%)  1/1863 (0.05%) 
Chronic obstructive pulmonary disease  1  13/1863 (0.70%)  11/1863 (0.59%) 
Dyspnoea  1  4/1863 (0.21%)  7/1863 (0.38%) 
Dyspnoea exertional  1  2/1863 (0.11%)  0/1863 (0.00%) 
Epistaxis  1  3/1863 (0.16%)  2/1863 (0.11%) 
Haemoptysis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Haemothorax  1  1/1863 (0.05%)  0/1863 (0.00%) 
Idiopathic pulmonary fibrosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Lung disorder  1  0/1863 (0.00%)  2/1863 (0.11%) 
Organising pneumonia  1  0/1863 (0.00%)  1/1863 (0.05%) 
Paranasal cyst  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pleural effusion  1  5/1863 (0.27%)  2/1863 (0.11%) 
Pleuritic pain  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pneumonia aspiration  1  3/1863 (0.16%)  2/1863 (0.11%) 
Pneumonitis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pneumothorax  1  3/1863 (0.16%)  3/1863 (0.16%) 
Pulmonary arterial hypertension  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pulmonary congestion  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pulmonary embolism  1  4/1863 (0.21%)  5/1863 (0.27%) 
Pulmonary fibrosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Pulmonary hypertension  1  3/1863 (0.16%)  2/1863 (0.11%) 
Pulmonary oedema  1  1/1863 (0.05%)  1/1863 (0.05%) 
Respiratory acidosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Respiratory failure  1  5/1863 (0.27%)  2/1863 (0.11%) 
Sleep apnoea syndrome  1  2/1863 (0.11%)  0/1863 (0.00%) 
Vocal cord thickening  1  1/1863 (0.05%)  0/1863 (0.00%) 
Skin and subcutaneous tissue disorders     
Actinic keratosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Angioedema  1  3/1863 (0.16%)  0/1863 (0.00%) 
Dermatitis bullous  1  0/1863 (0.00%)  1/1863 (0.05%) 
Diabetic foot  1  2/1863 (0.11%)  6/1863 (0.32%) 
Eczema  1  0/1863 (0.00%)  1/1863 (0.05%) 
Pemphigoid  1  0/1863 (0.00%)  1/1863 (0.05%) 
Skin ulcer  1  3/1863 (0.16%)  4/1863 (0.21%) 
Stasis dermatitis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Surgical and medical procedures     
Cardiac resynchronisation therapy  1  0/1863 (0.00%)  1/1863 (0.05%) 
Cardioversion  1  1/1863 (0.05%)  0/1863 (0.00%) 
Coronary arterial stent insertion  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hip arthroplasty  1  2/1863 (0.11%)  0/1863 (0.00%) 
Implantable defibrillator insertion  1  1/1863 (0.05%)  0/1863 (0.00%) 
Percutaneous coronary intervention  1  0/1863 (0.00%)  1/1863 (0.05%) 
Vascular disorders     
Aortic aneurysm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Aortic dissection  1  1/1863 (0.05%)  0/1863 (0.00%) 
Aortic intramural haematoma  1  1/1863 (0.05%)  0/1863 (0.00%) 
Aortic stenosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Arterial thrombosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Arteriosclerosis  1  2/1863 (0.11%)  0/1863 (0.00%) 
Bleeding varicose vein  1  1/1863 (0.05%)  0/1863 (0.00%) 
Circulatory collapse  1  5/1863 (0.27%)  0/1863 (0.00%) 
Deep vein thrombosis  1  5/1863 (0.27%)  4/1863 (0.21%) 
Diabetic vascular disorder  1  1/1863 (0.05%)  0/1863 (0.00%) 
Dry gangrene  1  0/1863 (0.00%)  1/1863 (0.05%) 
Embolism  1  0/1863 (0.00%)  1/1863 (0.05%) 
Extremity necrosis  1  1/1863 (0.05%)  2/1863 (0.11%) 
Femoral artery embolism  1  0/1863 (0.00%)  1/1863 (0.05%) 
Hypertension  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hypertensive crisis  1  4/1863 (0.21%)  6/1863 (0.32%) 
Hypertensive emergency  1  1/1863 (0.05%)  0/1863 (0.00%) 
Hypertensive urgency  1  1/1863 (0.05%)  1/1863 (0.05%) 
Hypotension  1  13/1863 (0.70%)  14/1863 (0.75%) 
Hypovolaemic shock  1  1/1863 (0.05%)  0/1863 (0.00%) 
Intermittent claudication  1  0/1863 (0.00%)  1/1863 (0.05%) 
Leriche syndrome  1  0/1863 (0.00%)  2/1863 (0.11%) 
Lymphocele  1  1/1863 (0.05%)  0/1863 (0.00%) 
Orthostatic hypotension  1  1/1863 (0.05%)  4/1863 (0.21%) 
Peripheral arterial occlusive disease  1  4/1863 (0.21%)  7/1863 (0.38%) 
Peripheral artery aneurysm  1  0/1863 (0.00%)  1/1863 (0.05%) 
Peripheral artery stenosis  1  1/1863 (0.05%)  1/1863 (0.05%) 
Peripheral artery thrombosis  1  0/1863 (0.00%)  1/1863 (0.05%) 
Peripheral embolism  1  2/1863 (0.11%)  0/1863 (0.00%) 
Peripheral ischaemia  1  4/1863 (0.21%)  5/1863 (0.27%) 
Peripheral vascular disorder  1  0/1863 (0.00%)  1/1863 (0.05%) 
Shock haemorrhagic  1  0/1863 (0.00%)  1/1863 (0.05%) 
Subclavian artery occlusion  1  1/1863 (0.05%)  1/1863 (0.05%) 
Subclavian vein occlusion  1  1/1863 (0.05%)  0/1863 (0.00%) 
Subgaleal haemorrhage  1  0/1863 (0.00%)  1/1863 (0.05%) 
Thrombosis  1  1/1863 (0.05%)  0/1863 (0.00%) 
Vascular insufficiency  1  0/1863 (0.00%)  1/1863 (0.05%) 
1
Term from vocabulary, MedDRA 23.0
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   369/1863 (19.81%)   328/1863 (17.61%) 
Infections and infestations     
Nasopharyngitis  1  94/1863 (5.05%)  89/1863 (4.78%) 
Metabolism and nutrition disorders     
Hyperkalaemia  1  109/1863 (5.85%)  99/1863 (5.31%) 
Hyperuricaemia  1  115/1863 (6.17%)  63/1863 (3.38%) 
Vascular disorders     
Hypotension  1  109/1863 (5.85%)  120/1863 (6.44%) 
1
Term from vocabulary, MedDRA 23.0
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, Call Centre
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03057977    
Other Study ID Numbers: 1245.121
2016-002280-34 ( EudraCT Number )
First Submitted: February 16, 2017
First Posted: February 20, 2017
Results First Submitted: April 26, 2021
Results First Posted: May 18, 2021
Last Update Posted: May 18, 2021