Heart Failure
Conditions
Brief summary
This is a study in adults who are in hospital for acute heart failure. The purpose of this study is to find out whether starting to take a medicine called empagliflozin soon after first being treated in hospital helps people with acute heart failure. Participants are in the study for about 3 months. At the beginning, participants are still in hospital. Later, they visit the hospital about 3 times and get 1 phone call. Participants are put into 2 groups by chance. One group takes 1 empagliflozin tablet a day. The other group takes 1 placebo tablet a day. Placebo tablets look like empagliflozin tablets but do not contain any medicine. Empagliflozin belongs to a class of medicines known as SGLT-2 inhibitors. It is used to treat type 2 diabetes. During the study, the doctors check whether participants have additional heart failure events like needing to go to the hospital again because of heart failure. The participants answer questions about how their heart failure affects their life. We then compare the results between the empagliflozin and placebo groups. The doctors also regularly check the general health of the participants.
Interventions
DRUGEmpagliflozin
Film-coated tablet
Film-coated tablet
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
* Currently hospitalised for the primary diagnosis of acute heart failure (de novo or decompensated chronic HF), regardless of ejection fraction (EF). Patients with a diagnosis of hospitalized heart failure must have HF symptoms at the time of hospital admission * Evidence of left ventricular ejection fraction (LVEF, either reduced or preserved EF) as per local reading preferably measured during current hospitalisation or in the 12 months prior to randomisation * Patients must be randomised after at least 24 hours and no later than 5 days after admission, as early as possible after stabilization and while still in hospital * Patients must fulfil the following stabilisation criteria (while in the hospital): * SBP ≥100mm Hg and no symptoms of hypotension in the preceding 6 hours, * no increase in i.v. diuretic dose for 6 hours prior to randomisation, * no i.v. vasodilators including nitrates within the last 6 hours prior to randomisation * no i.v. inotropic drugs for 24 hours prior to randomisation. * Elevated NT-proBNP ≥ 1600pg/mL or BNP ≥400 pg/mL according to the local lab, for patients without atrial fibrillation (AF); or elevated NT-proBNP ≥ 2400pg/mL or BNP ≥600 pg/mL for patients with AF, measured during the current hospitalization or in the 72 hours prior to hospital admission,. For patients treated with an angiotensin receptor neprilysin inhibitor (ARNI) in the previous 4 weeks prior to randomisation, only NT-proBNP values should be used * HF episode leading to hospitalisation must have been treated with a minimum single dose of 40 mg of i.v. furosemide (or equivalent i.v. loop diuretic defined as 20 mg of torasemide or 1 mg of bumetanide) * Further Inclusion Criteria Apply
Exclusion criteria
* Cardiogenic shock * Current hospitalisation for acute heart failure primarily triggered by pulmonary embolism, cerebrovascular accident, or acute myocardial infarction (AMI) * Current hospitalisation for acute heart failure not caused primarily by intravascular volume overload; * Below interventions in the past 30 days prior to randomisation or planned during the study: * Major cardiac surgery, or TAVI (Transcatheter Aortic Valve Implantation), or PCI, or Mitraclip * All other surgeries that are considered major according to investigator judgement * Implantation of cardiac resynchronisation therapy (CRT) device * cardiac mechanical support implantation * Carotid artery disease revascularisation (stent or surgery) * Acute coronary syndrome / myocardial infarction, stroke or transient ischemic attack (TIA) in the past 90 days prior to randomisation * Heart transplant recipient, or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement), or planned for palliative care for HF, or currently using left ventricular assist device (LVAD) or intra-aortic balloon pump (IABP) or any other type of mechanical circulatory support, or patients on mechanical ventilation, or patients with planned inotropic support in an outpatient setting * Haemodynamically significant (severe) uncorrected primary cardiac valvular disease planned for surgery or intervention during the course of the study (note: secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study) * Impaired renal function, defined as eGFR \< 20 mL/min/1.73 m2 as measured during hospitalization (latest local lab measurement before randomisation) or requiring dialysis * Type 1 Diabetes Mellitus (T1DM) * History of ketoacidosis, including diabetic ketoacidosis (DKA) * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Pairwise Comparisons With Wins of Clinical Benefit, a Composite of Death, Number of Heart Failure Events (HFEs), Time to the First HFE and ≥5-point Difference in CfB in KCCQ-TSS After 90 Days of Treatment | Up to 90 days. For KCCQ-TSS: at baseline and at day 90. | Clinical benefit, a composite of death, number of HFEs, time to first HFE and change from baseline (CfB) in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) after 90 days of treatment. All patients randomised to empagliflozin are compared to all patients randomised to placebo within strata. For any two patients, a patient will win, i.e. achieve a better clinical outcome, as determined by assessing the following criteria sequentially, stopping when an advantage for either patient is shown: 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in KCCQ-TSS After 90 Days of Treatment | At baseline, at day 15, 30 and at day 90. | Change from baseline in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS). The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire that includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. The symptom frequency and symptom burden domains are merged into the total symptom score. The score is represented on a 0-to-100-point scale, where a higher score reflects a better health status. Change from baseline in KCCQ-TSS at day 90 was modeled using a MMRM with visit (day 15 and day 30) as repeated measures, adjusted mean (standard error) after 90 days of treatment is reported. |
| Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment | From baseline to day 30. | Change from baseline in log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area under the curve (AUC) over 30 days of treatment is reported. |
| Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge | Up to 30 days after initial hospital discharge. | The follow-up time for DAOH analyses was defined as 30 days after initial hospital discharge, or time between initial hospital discharge and date of censoring for non-fatal events except for patients who died within the first 30 days, where 30 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 30 days after initial hospital discharge as well as the number of days being dead within the 30 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100. |
| Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation | Up to 90 days after randomisation. | The follow-up time for DAOH analyses was defined as 90 days after randomisation, or time between randomisation and date of censoring for non-fatal events except for patients who died within the first 90 days, where 90 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 90 days after randomisation as well as the number of days being dead within the first 90 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100. |
| Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment | At baseline and at day 90. | Number of participants with improvement of at least 10 points in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS) from baseline after 90 days of treatment. The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire that includes 23 items that map to 7 domains: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. The symptom frequency and symptom burden domains are merged into the total symptom score. Scores are represented on a 0-to-100-point scale, where a higher score reflects a better health status. |
| Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge | Up to 30 days after initial hospital discharge. | Number of participants with hospitalization for heart failure (HHF) until 30 days after initial hospital discharge. |
| Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr | Up to 90 days. | The occurrence of the composite renal endpoint: * chronic dialysis (with a frequency of twice per week or more for at least 90 days), or * renal transplant, or * sustained reduction in Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) from baseline of ≥40%, or * sustained eGFR \[mL/min/1.73 m2\] \<15 and baseline value ≥30, or * sustained eGFR \<10 and baseline value \<30; is reported by number of participants with component events. (These events may have occurred after the endpoint was already met. Combinations may not have occurred on the same day). Sustained was determined by 2 or more consecutive post-baseline central laboratory measurements separated by at least 30 days. |
| Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment | At baseline and at day 15. | Diuretic effect as assessed by weight change per mean daily loop diuretic dose after 15 days of treatment. Diuretic dose = 40 mg intravenous furosemide or 80 mg oral furosemide. Abbreviation: Kg: Kilogram |
| Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment | At baseline and at day 30. | Diuretic effect as assessed by weight change per mean daily loop diuretic dose after 30 days of treatment. Diuretic dose = 40 mg intravenous furosemide or 80 mg oral furosemide Abbreviation: Kg: Kilogram |
| Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit | Up to 127 days. | Incidence rate of first occurrence of CV death or HFE until end of trial visit per 100 patient-year (pt-yrs) at risk is reported. Incidence rate per 100 pt-yrs = 100\* number of patients with event / time at risk \[years\]. |
Countries
Belgium, Canada, China, Czechia, Denmark, Germany, Hungary, Italy, Japan, Netherlands, Norway, Poland, Spain, Sweden, United States
Participant flow
Recruitment details
A multicentre, randomised, double-blind trial to assess whether in-hospital administration of empagliflozin results in improvement in heart failure-related outcomes compared to placebo in patients with acute heart failure.
Pre-assignment 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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 1 film-coated tablet of placebo matching 10 mg empagliflozin was administered orally once daily in patients with acute heart failure. | 265 |
| 10 mg Empagliflozin 1 film-coated tablet of 10 milligram (mg) of empagliflozin was administered orally once daily in patients with acute heart failure. | 265 |
| Total | 530 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 34 | 23 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Not treated | 1 | 5 |
| Overall Study | Other reason not stated above | 10 | 10 |
| Overall Study | Withdrawal by Subject | 12 | 17 |
Baseline characteristics
| Characteristic | Placebo | 10 mg Empagliflozin | Total |
|---|---|---|---|
| Age, Continuous | 68.1 Years STANDARD_DEVIATION 13.8 | 68.9 Years STANDARD_DEVIATION 12.6 | 68.5 Years STANDARD_DEVIATION 13.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 256 Participants | 259 Participants | 515 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Kansas City cardiomyopathy questionnaire-Total symptom score (KCCQ-TSS) | 41.91 Score on a scale STANDARD_DEVIATION 23.98 | 39.71 Score on a scale STANDARD_DEVIATION 24.06 | 40.81 Score on a scale STANDARD_DEVIATION 24.02 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 32 Participants | 57 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 21 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 202 Participants | 211 Participants | 413 Participants |
| Sex: Female, Male Female | 93 Participants | 86 Participants | 179 Participants |
| Sex: Female, Male Male | 172 Participants | 179 Participants | 351 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 265 | 11 / 265 |
| other Total, other adverse events | 19 / 264 | 20 / 260 |
| serious Total, serious adverse events | 115 / 264 | 84 / 260 |
Outcome results
Primary
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
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.
Population: Randomised Set (RS), including all randomised patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Time to death | 4.01 pct. (%) of winning pairwise comparisons |
| Placebo | 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 | Frequency of HFEs | 7.65 pct. (%) of winning pairwise comparisons |
| Placebo | 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 | Time to HFE | 0.57 pct. (%) of winning pairwise comparisons |
| Placebo | 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 | KCCQ-TSS change from baseline (>=5-point difference) | 27.48 pct. (%) of winning pairwise comparisons |
| 10 mg Empagliflozin | 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 | KCCQ-TSS change from baseline (>=5-point difference) | 35.91 pct. (%) of winning pairwise comparisons |
| 10 mg Empagliflozin | 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 | Time to death | 7.15 pct. (%) of winning pairwise comparisons |
| 10 mg Empagliflozin | 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 | Time to HFE | 0.24 pct. (%) of winning pairwise comparisons |
| 10 mg Empagliflozin | 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 | Frequency of HFEs | 10.59 pct. (%) of winning pairwise comparisons |
Comparison: 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 empap-value: 0.002795% CI: [1.09, 1.68]Asymptotic normal U statistics approach
Secondary
Change From Baseline in KCCQ-TSS After 90 Days of Treatment
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.
Population: Patients in the randomised set (RS) and with non-missing data for this endpoint. Observed case including data after treatment discontinuation (OC-AD).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in KCCQ-TSS After 90 Days of Treatment | 31.73 Score on a scale | Standard Error 1.49 |
| 10 mg Empagliflozin | Change From Baseline in KCCQ-TSS After 90 Days of Treatment | 36.19 Score on a scale | Standard Error 1.48 |
Comparison: 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.p-value: 0.034795% CI: [0.32, 8.59]Mixed Models Analysis
Secondary
Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment
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.
Population: Patients included the randomised set (RS), and with non-missing data for this endpoint.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment | 26.77 Picogram/milliliter * days |
| 10 mg Empagliflozin | Change From Baseline in Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment | 24.07 Picogram/milliliter * days |
Comparison: 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.p-value: 0.017695% CI: [0.82, 0.98]ANCOVA
Secondary
Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr
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.
Population: Randomised Set (RS), including all randomised patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr | 2 Participants |
| 10 mg Empagliflozin | Composite Renal Endpoint: Number of Participants With Chronic Dialysis, Renal Transplant, Sustained Reduction in eGFR(CKD-EPI)cr | 0 Participants |
Secondary
Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit
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.
Population: Randomised Set (RS), including all randomised patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit | 78.81 Patients with events / 100pt-yrs at risk |
| 10 mg Empagliflozin | Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit | 55.01 Patients with events / 100pt-yrs at risk |
p-value: 0.124195% CI: [0.46, 1.1]Regression, Cox
Secondary
Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge
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.
Population: Randomised Set (RS), including all randomised patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge | 12 Participants |
| 10 mg Empagliflozin | Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge | 14 Participants |
Secondary
Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment
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.
Population: Randomised Set (RS), including all randomised patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment | 202 Participants |
| 10 mg Empagliflozin | Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment | 220 Participants |
Comparison: Logistic regression including terms for baseline KCCQ-TSS, treatment and heart failure statusp-value: 0.09795% CI: [0.927, 2.501]Regression, Logistic
Secondary
Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge
The follow-up time for DAOH analyses was defined as 30 days after initial hospital discharge, or time between initial hospital discharge and date of censoring for non-fatal events except for patients who died within the first 30 days, where 30 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 30 days after initial hospital discharge as well as the number of days being dead within the 30 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100.
Time frame: Up to 30 days after initial hospital discharge.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge | 80.90 DAOH in percentage (%) | Standard Deviation 21.25 |
| 10 mg Empagliflozin | Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 30 Days After Initial Hospital Discharge | 81.37 DAOH in percentage (%) | Standard Deviation 18.62 |
Secondary
Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation
The follow-up time for DAOH analyses was defined as 90 days after randomisation, or time between randomisation and date of censoring for non-fatal events except for patients who died within the first 90 days, where 90 days was considered as the DAOH follow-up time. DAOH for each patient was calculated as follow-up time subtracted by the number of days in hospital during the 90 days after randomisation as well as the number of days being dead within the first 90 days. Percentage DAOH was defined as DAOH divided by the DAOH follow-up time of each patient multiplied by 100.
Time frame: Up to 90 days after randomisation.
Population: Patients in the treated set (TS) and with non-missing data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation | 85.79 DAOH in percentage (%) | Standard Deviation 22.76 |
| 10 mg Empagliflozin | Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation | 87.55 DAOH in percentage (%) | Standard Deviation 19.54 |
Secondary
Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment
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.
Population: Patients in the randomised set (RS) and with non-missing values for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment | -2.43 Kg per loop diuretic dose | Standard Deviation 23.46 |
| 10 mg Empagliflozin | Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment | -4.45 Kg per loop diuretic dose | Standard Deviation 16.65 |
Secondary
Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment
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.
Population: Patients in the randomised set (RS) and with non-missing values for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment | -2.69 Kg per loop diuretic dose | Standard Deviation 21.74 |
| 10 mg Empagliflozin | Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment | -6.91 Kg per loop diuretic dose | Standard Deviation 25.34 |