Health Condition 1: I509- Heart failure, unspecified
Conditions
Interventions
Intervention1: BI 690517
: Dose: 1 tablet once daily
Route: oral
Duration: 148 weeks
Control Intervention1: Placebo matching BI 690517: Dose: 1 tablet once daily
Route: oral
Duration: 148 weeks
Contr
Sponsors
Boehringer Ingelheim International GmbH
IQVIA RDS INDIA PRIVATE LIMITED
Eligibility
Inclusion criteria
Inclusion criteria: Eligible participants will have a diagnosis of HF with LVEF 40 percent and meet eligibility criteria below. 1. At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years 2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial 3. Male or female participants. Women of childbearing potential1 must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1percent per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information. 4. Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA class II-IV at Visit 1, with LVEF 40 percent per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, MRI, or CT). A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before Visit 2 (if several values are available, the most recent one should be considered) 5. Presence of structural heart abnormality (confirmed by any imaging modality; i.e. echocardiography at Visit 1, as defined by left ventricular hypertrophy or left atrial enlargement) (see Appendix 10.3). Historical imaging may be used if performed within 12 months prior to Visit 1, or imaging may be completed after study consent has been obtained and before Visit 2. If several values are available, the most recent one should be considered. 6. At least one of the following: (a) Currently treated with diuretic therapy e.g. loop diuretics or thiazides, and on a stable dose for at least 1 week prior to Visit 1 (b) Documented hospitalisation for HF within 6 months prior to Visit 1 (c) Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1 (a). in participants without Afib or Aflutter (at Visit 1 ECG): 900 pg/mL (b). for participants with Afib or Aflutter (at Visit 1 ECG): 1800 pg/mL 7. Participants must be treated according to best possible SOC in accordance with applicable HF local/international guidelines (according to the judgment of the investigator) Additional inclusion criteria apply to the optional accelerometry substudy: (1) Willing and able to provide informed consent for substudy participation; and (2) Capable of ambulation, with or without a walking aid. 8. Elevated NTproBNP at Visit 1, analysed at the central laboratory at Visit 1 a) n participants with BMI less than 27 kg/m2 more than equals to 300 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG), (b) in participants with BMI more than equals to 27 kg/m2 to less than 35 kg/m2 more than equals to 220 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 660 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG) (c) in participants with BMI more than equals to 35 kg/m2 more than equals to 125 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)
Exclusion criteria
Exclusion criteria: 1. Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator. Treatment with MRA should not be interrupted with the intention of enrolment into the study 2. Treatment with amiloride, or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator 3. Receiving the following treatments: a. a direct renin inhibitor (e.g. aliskiren) at Visit 2 b. more than one ACEI, ARB or ARNI, or two simultaneously at Visit 2 c. Acute decompensated HF requiring hospitalisation or i.v. therapy including diuretics, or i.v. inotropes or i.v. vasodilators, mechanical support (such as an intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device), or IV natriuretic peptide (e.g. nesiritide) within the past 7 days prior to Visit 2 4. MI, CVA, TIA, stroke, coronary artery bypass graft surgery/CABG, heart valve surgery or any other major surgery (major according to the investigator assessment) within 90 days prior to Visit 1, or scheduled for major elective surgery (e.g. hip replacement, coronary artery bypass graft surgery/CABG) 5. Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD 6. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to Visit 1 and until Visit 2 7. Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1and until Visit 2 8. Known severe valvular heart disease (obstructive or regurgitant), as per investigator judgment, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study 9. Atrial fibrillation or Atrial flutter with a resting heart rate more than 110 bpm documented by ECG at Visit 1 10. Untreated clinically relevant ventricular arrhythmia without an ICD at Visit 1 and/or Visit 2 11. Unless managed with an implanted pacemaker: symptomatic bradycardia, sick sinus syndrome, Mobitz Type II second degree AV-Block, or third-degree heart block 12. Implantation of ICD or CRT within 3 months prior to Visit 1 or until Visit 2 13. Symptomatic hypotension and/or a SBP less than 100 mmHg at Visit 1 or Visit 2 14. SBP more than equals to 180 mmHg at Visit 1 or Visit 2. If SBP more than 150 mmHg and less than 180 mmHg at Visit 1, the participant should be receiving at least 3 antihypertensive drugs. 15. Severe chronic pulmonary disease according to investigators judgment: e.g. with known FEV1 less than 50 percent or need for home oxygen, primary pulmonary arterial hypertension, or chronic obstructive pulmonary disease exacerbation requiring i.v. or chronic oral steroids within 3 months prior to Visit 1 or until Visit 2 16. Serum potassium more than 5.2 mmol/L measured by the central laboratory at Visit 1 (Note on
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the superiority of the combination of BI 690517 10 mg and empagliflozin 10 mg compared with placebo and empagliflozin 10 mg for the time to first CV death or HHF in participants with HF and LVEF more than equals to 40%, based on a hazard ratioTimepoint: Time to first event of CV death or HHF. Death and HHF will be categorised by the investigator according to pre-specified criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| to demonstrate the superiority of the combination of BI 690517 10 mg & empagliflozin 10 mg to placebo & empagliflozin 10 mg for the time to first event of CV death, HHF or urgent HF visit, the total number of HHF (first & recurrent), the absolute change from baseline in KCCQ-TSS at Week 32 [R17-2666], the time to CV death & the time to all-cause mortalityTimepoint: Time to first event of CV death, HHF or urgent heart failure visit Occurrences of HHFs (first & recurrent) Absolute change from baseline in KCCQ-TSS at Week 32 Time to CV death Time to all-cause mortality | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Poland, Republic of Korea, Romania, Saudi Arabia, Serbia, Slovenia, South Africa, Spain, Taiwan, Turkey, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed