A Multicentre, Randomised, Double-blind, 90-day Superiority Trial to Evaluate the Effect on Clinical Benefit, Safety and Tolerability of Once Daily Oral EMPagliflozin 10 mg Compared to Placebo, Initiated in Patients Hospitalised for acUte Heart faiLure (de Novo or Decompensated Chronic HF) Who Have Been StabilisEd (EMPULSE)
Overview
- Phase
- Phase 3
- Intervention
- Empagliflozin
- Conditions
- Heart Failure
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 530
- Locations
- 118
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
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)
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
Arms & Interventions
Empagliflozin
Intervention: Empagliflozin
Placebo
Intervention: Placebo to Empagliflozin
Outcomes
Primary Outcomes
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 Frame: 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 Outcomes
- Incidence Rate of First Occurrence of Cardiovascular (CV) Death or Heart Failure Event (HFE) Until End of Trial Visit(Up to 127 days.)
- Number of Participants With Improvement of at Least 10 Points in KCCQ-TSS After 90 Days of Treatment(At baseline and at day 90.)
- 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 Log-transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) Area Under the Curve (AUC) Over 30 Days of Treatment(From baseline to day 30.)
- 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.)
- Percentage of Days Alive and Out of Hospital (DAOH) From Study Drug Initiation Until 90 Days After Randomisation(Up to 90 days after randomisation.)
- Number of Participants With Hospitalization for Heart Failure (HHF) Until 30 Days After Initial Hospital Discharge(Up to 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.)
- Weight Change Per Mean Daily Loop Diuretic Dose After 15 Days of Treatment(At baseline and at day 15.)
- Weight Change Per Mean Daily Loop Diuretic Dose After 30 Days of Treatment(At baseline and at day 30.)