Trial Outcomes & Findings for A Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure (NCT NCT04157751)

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.

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.

Only participants in the randomised set and with non-missing data are included.

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

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.

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 is reported.

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.

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.

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 \[years\].

Number of participants with hospitalization for heart failure (HHF) until 30 days after initial hospital discharge.

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.

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

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