Heart Failure
Conditions
Brief summary
The aim of the study is to investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.
Interventions
DRUGEmpagliflozin
once daily
DRUGPlacebo
once daily
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient age \>= 18 years at screening. For Japan only: Age \>= 20 years at screening * Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association Classification) class II-IV and reduced EF (Ejection Fraction) (LVEF (Left Ventricular Ejection Fraction) \<=40%) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide) * If EF \>= 36% to \<= 40%: NT-proBNP \>= 2500 pg/ml or patients without AF (atrial fibrillation/atrial flutter) and NT-proBNP \>= 5000 pg/ml for patients with AF * If EF \>= 31% to \<= 35%: NT-proBNP \>= 1000 pg/ml for patients without AF and NT-proBNP \>=2000 pg/ml for patients with AF * If EF\<= 30%: NT-proBNP \>= 600 pg/ml for patients without AF and NT-proBNP \>=1200 pg/ml for patients with AF * EF ≤ 40% and hospitalization for heart failure in the past 12 months: NTproBNP ≥ 600 pg/ml for patients without AF and NT-proBNP \>= 1200 pg/ml for patients with AF * Appropriate dose of medical therapy for HF consistent with prevailing local and international CV (Cardiovascular) guidelines, stable for at least 1 week prior to Visit 1 * Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines * Signed and dated written ICF (Informed Consent Form) * Further inclusion criteria apply
Exclusion criteria
* Myocardial infarction, coronary artery bypass graft surgery, or other major cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days prior to Visit 1 * Heart transplant recipient, or listed for heart transplant * Acute decompensated HF * Systolic blood pressure (SBP) \>= 180 mmHg at Visit 2. * Symptomatic hypotension and/or a SBP \< 100 mmHg * Indication of liver disease * Impaired renal function, defined as eGFR (Estimated Glomerular Filtration Rate) \< 20 mL/min/1.73 m2 (CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration Equation)) or requiring dialysis * History of ketoacidosis * Current use or prior use of a SGLT (Sodium-glucose co-transporter)-2 inhibitor or combined SGLT-1 and 2 inhibitor * Currently enrolled in another investigational device or drug study * Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors * Women who are pregnant, nursing, or who plan to become pregnant while in the trial * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF) | From randomisation until completion of the planned treatment period, up to 1040 days. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| eGFR (CKD-EPI) cr Slope of Change From Baseline | Assessed at baseline, week 4, 12, 32, 52, 76, 100, 124, 148 and at end of treatment (EOT), up to 1040 days. | 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 to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr | From randomisation until completion of the planned treatment period, up to 1040 days. | 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 to First Adjudicated Hospitalisation for Heart Failure (HHF) | From randomisation until completion of the planned treatment period, up to 1040 days. | 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 to Adjudicated Cardiovascular (CV) Death | From randomisation until completion of the planned treatment period, up to 1040 days. | 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. |
| Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent) | From randomisation until completion of the planned treatment phase, up to 1040 days. | 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 to Onset of Diabetes Mellitus (DM) | From randomisation until completion of the planned treatment period, up to 1040 days. | 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. |
| Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52 | Assessed at baseline, week 12, week 32 and week 52. | 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. |
| Number of All-cause Hospitalizations (First and Recurrent) | From randomisation until completion of the planned treatment phase, up to 1040 days. | Number of all-cause hospitalizations (first and recurrent). |
| Time to All-cause Mortality | From randomisation until completion of the planned treatment period, up to 1040 days. | 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. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 1 film-coated tablet of matching placebo was administered orally once daily. | 1,867 |
| 10 mg Empagliflozin Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. | 1,863 |
| Total | 3,730 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Discontinuation From Treatment | Adverse Event | 343 | 337 |
| Discontinuation From Treatment | Due to Covid-19 Pandemic | 1 | 4 |
| Discontinuation From Treatment | Lost to Follow-up | 11 | 17 |
| Discontinuation From Treatment | Not attending study visit | 3 | 10 |
| Discontinuation From Treatment | Not treated | 4 | 0 |
| Discontinuation From Treatment | Other medical condition (no Adverse Event) | 2 | 4 |
| Discontinuation From Treatment | Patient decision to stop/interrupt medication | 8 | 6 |
| Discontinuation From Treatment | Patient moved away/being abroad | 4 | 3 |
| Discontinuation From Treatment | Patient received Empagliflozin for Diabetes | 1 | 1 |
| Discontinuation From Treatment | Personal Reasons | 1 | 1 |
| Discontinuation From Treatment | Principle Investigator Decision | 2 | 0 |
| Discontinuation From Treatment | Protocol Violation | 6 | 5 |
| Discontinuation From Treatment | Reason Unknown | 0 | 1 |
| Discontinuation From Treatment | Unable to continue treatment | 4 | 1 |
| Discontinuation From Treatment | Unblinded medication | 1 | 0 |
| Discontinuation From Treatment | Withdrawal by Subject | 124 | 92 |
| Discontinuation From Trial | Limited follow-up agreed | 2 | 2 |
| Discontinuation From Trial | Lost to follow-up to primary endpoint | 9 | 9 |
| Discontinuation From Trial | Withdrawal by Subject | 9 | 11 |
Baseline characteristics
| Characteristic | 10 mg Empagliflozin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 67.2 Years STANDARD_DEVIATION 10.8 | 66.8 Years STANDARD_DEVIATION 11 | 66.5 Years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 616 Participants | 1229 Participants | 613 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1164 Participants | 2342 Participants | 1178 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 83 Participants | 159 Participants | 76 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 15 Participants | 39 Participants | 24 Participants |
| Race (NIH/OMB) Asian | 337 Participants | 672 Participants | 335 Participants |
| Race (NIH/OMB) Black or African American | 123 Participants | 257 Participants | 134 Participants |
| Race (NIH/OMB) More than one race | 28 Participants | 61 Participants | 33 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 27 Participants | 58 Participants | 31 Participants |
| Race (NIH/OMB) White | 1325 Participants | 2629 Participants | 1304 Participants |
| Sex: Female, Male Female | 437 Participants | 893 Participants | 456 Participants |
| Sex: Female, Male Male | 1426 Participants | 2837 Participants | 1411 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 266 / 1,867 | 249 / 1,863 |
| other Total, other adverse events | 369 / 1,863 | 328 / 1,863 |
| serious Total, serious adverse events | 896 / 1,863 | 772 / 1,863 |
Outcome results
Primary
Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF)
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.
Population: Randomised Set: All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF) | 21.00 Patients with events/ 100 pt-yrs at risk |
| 10 mg Empagliflozin | Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF) | 15.77 Patients with events/ 100 pt-yrs at risk |
Comparison: 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.p-value: <0.000195.04% CI: [0.65, 0.86]Regression, Cox
Secondary
Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52
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.
Population: Patients in the randomized set (RS) with available data for this endpoint, including values obtained on treatment or post-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52 | -3.36 Score on a scale | Standard Error 0.69 |
| 10 mg Empagliflozin | Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52 | -1.30 Score on a scale | Standard Error 0.69 |
Comparison: 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.p-value: 0.03495% CI: [0.16, 3.96]Mixed Model
Secondary
eGFR (CKD-EPI) cr Slope of Change From Baseline
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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | eGFR (CKD-EPI) cr Slope of Change From Baseline | -2.278 Milliliter/minute/1.73 meters squared | Standard Error 0.229 |
| 10 mg Empagliflozin | eGFR (CKD-EPI) cr Slope of Change From Baseline | -0.546 Milliliter/minute/1.73 meters squared | Standard Error 0.227 |
Comparison: 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=0.001p-value: <0.000199.9% CI: [0.669, 2.796]Random intercept random coef. model
Secondary
Number of All-cause Hospitalizations (First and Recurrent)
Number of all-cause hospitalizations (first and recurrent).
Time frame: From randomisation until completion of the planned treatment phase, up to 1040 days.
Population: Randomised Set: All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of All-cause Hospitalizations (First and Recurrent) | 1570 Hospitalizations for any cause |
| 10 mg Empagliflozin | Number of All-cause Hospitalizations (First and Recurrent) | 1364 Hospitalizations for any cause |
Comparison: 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.p-value: 0.006595% CI: [0.75, 0.95]Joint frailty model
Secondary
Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent)
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.
Population: Randomised Set (RS): All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent) | 553 HHF events |
| 10 mg Empagliflozin | Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent) | 388 HHF events |
Comparison: 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.p-value: 0.000395.04% CI: [0.58, 0.85]Joint frailty model
Secondary
Time to Adjudicated Cardiovascular (CV) Death
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.
Population: Randomised Set: All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to Adjudicated Cardiovascular (CV) Death | 8.13 Patients with events/ 100 pt-yrs at risk |
| 10 mg Empagliflozin | Time to Adjudicated Cardiovascular (CV) Death | 7.55 Patients with events/ 100 pt-yrs at risk |
p-value: 0.413395% CI: [0.75, 1.12]Regression, Cox
Secondary
Time to All-cause Mortality
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.
Population: Randomised Set: All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to All-cause Mortality | 10.71 Patients with events/ 100 pt-yrs at risk |
| 10 mg Empagliflozin | Time to All-cause Mortality | 10.06 Patients with events/ 100 pt-yrs at risk |
p-value: 0.353695% CI: [0.77, 1.1]Regression, Cox
Secondary
Time to First Adjudicated Hospitalisation for Heart Failure (HHF)
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.
Population: Randomised Set (RS): All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to First Adjudicated Hospitalisation for Heart Failure (HHF) | 15.55 Patients with events/ 100 pt-yrs at risk |
| 10 mg Empagliflozin | Time to First Adjudicated Hospitalisation for Heart Failure (HHF) | 10.75 Patients with events/ 100 pt-yrs at risk |
p-value: <0.000195% CI: [0.59, 0.81]Regression, Cox
Secondary
Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr
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.
Population: Randomised Set: All randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr | 3.07 Patients with events/ 100 pt-yrs at risk |
| 10 mg Empagliflozin | Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr | 1.56 Patients with events/ 100 pt-yrs at risk |
p-value: 0.001995% CI: [0.32, 0.77]Regression, Cox
Secondary
Time to Onset of Diabetes Mellitus (DM)
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.
Population: Patients in the randomised set with pre-DM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to Onset of Diabetes Mellitus (DM) | 10.62 Patients with events/ 100 pt-yrs at risk |
| 10 mg Empagliflozin | Time to Onset of Diabetes Mellitus (DM) | 9.31 Patients with events/ 100 pt-yrs at risk |
p-value: 0.357695% CI: [0.62, 1.19]Regression, Cox