heart failure
Conditions
Interventions
BI 690517 and empagliflozin,:BI 690517 and empagliflozin
Placebo and empagliflozin:placebo and empagliflozin
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 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 potential (WOCBP1.see Section 4.2.2.3)1 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 1% 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 in Section 4.2.2.3 4.Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA class II-IV at Visit 1, with LVEF >=40% 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; 2.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.Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1: (1) in participants with BMI =300 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and >=900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG) ; (2)in participants with BMI >=27 kg/m^2 to =220 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and >=660 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG) ; (3)in participants with BMI >=35 kg/m^2: >=125 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and >=375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG) ; 7.At least one of the following: (1)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 ; (2)Documented hospitalisation for HF within 6 months prior to Visit 1; (3)Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1 ; 1).in participants without Afib or Aflutter (at Visit 1 ECG): >=900 pg/mL ;2)for participants with Afib or Aflutter (at Visit 1 ECG): >=1800 pg/mL ; 8.Participants must be treated according to best possible SOC in accordance with applicable HF local/international guidelines (according to the judgment of the investigator);
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’s 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’s 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 >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 =180 mmHg at Visit 1 or Visit 2. If SBP >150 mmHg and 5.2 mmol/L measured by the central laboratory at Visit 1 (Note: one reassessment of serum potassium is allowed during screening); 17.ALT or AST >3x ULN at Visit 1 or known hepatic cirrhosis (Child Pugh C), or other liver disease causing severe impaired liver
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first event of CV death or HHF; | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to first event of CV death, HHF or urgent HF visit;Occurrences (first and recurrent) of HHF;Absolute change from baseline in KCCQ-TSS at Week 32;Time to all-cause mortality;Time to CV death; | — |
Countries
China
Contacts
Public ContactJuying Qian
Zhongshan Hospital, Fudan University
Outcome results
None listed