A Study to Test Whether BI 690517 in Combination With Empagliflozin Helps People With Heart Failure

Boehringer Ingelheim

Status and phase

Enrolling

Phase 3

Conditions

Heart Failure

Treatments

Drug: Empagliflozin

Drug: BI 690517

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT06424288

1378-0020

2023-509706-30-00 (Registry Identifier)

U1111-1302-4422 (Registry Identifier)

Details and patient eligibility

About

This study is open to adults aged 18 or above legal age with heart failure. People can join the study if they have heart failure symptoms and a left ventricular ejection fraction (LVEF) of 40% or more. The purpose of this study is to find out whether BI 690517 in combination with empagliflozin helps people with heart failure.

Participants are put into 2 groups by chance. Every participant has an equal chance of being in each group. The groups are:

BI 690517 and empagliflozin group: participants take BI 690517 and empagliflozin as tablets once a day.
Placebo and empagliflozin group: participants take placebo and empagliflozin as tablets once a day.

Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, they visit their doctors regularly. The doctors regularly check participants' health and take note of any unwanted effects. The study staff may also contact the participants by phone. Participants also regularly answer questions about their well-being.

The study does not have a fixed duration. It continues until we have enough data to see if the treatment is working.

Enrollment

6,000 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
Male or female participants. Women of childbearing potential (WOCBP) 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
Chronic Heart failure (HF) diagnosed at least 3 months before Visit 1, and in New York Heart Association (NYHA) class II-IV at Visit 1, with left ventricular ejection fraction (LVEF) ≥40% per local reading. 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
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). 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
Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysed at the central laboratory at Visit 1:
1. in participants with body mass index (BMI) <27 kg/m²: ≥300 pg/mL for participants without atrial fibrillation (Afib) or atrial flutter (Aflutter) (at Visit 1 electrocardiogram (ECG)) and ≥900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)
2. in participants with BMI ≥27 kg/m² to <35 kg/m²: ≥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/m²: ≥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)
At least one of the following:
- 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
- Documented hospitalisation for HF within 6 months prior to Visit 1
- Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1
  - in participants without Afib or Aflutter (at Visit 1 ECG): ≥900 pg/mL
  - for participants with Afib or Aflutter (at Visit 1 ECG): ≥1800 pg/mL
Participants must be treated according to best possible standard of care (SOC) in accordance with applicable HF local/international guidelines (according to the judgment of the investigator)

Exclusion criteria

Treatment with an mineralocorticoid receptor antagonist (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
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
Receiving the following treatments:
- a direct renin inhibitor (e.g. aliskiren) at Visit 2
- more than one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI), or two simultaneously at Visit 2
- 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
Myocardial infarction (MI), cerebrovascular accident (CVA), transient ischemic attack (TIA), stroke, coronary artery bypass graft (CABG) surgery, 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)
Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device (LVAD)
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
Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1 and until Visit 2
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 Further exclusion criteria apply.