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 vicadrostat (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:
* Vicadrostat/empagliflozin group: participants take vicadrostat/empagliflozin as tablets once a day.
* Placebo/empagliflozin group: participants take placebo/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 there is enough data to see if the treatment is working.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 (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
4. 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 randomisation at Visit 2
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). 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
6. 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)
7. 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
* Urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, analysed at the central laboratory at Visit 1
8. Treated according to best possible standard of care (SOC) (disregarding Sodium-dependent glucose co-transporter 2 inhibitors (SGLT2is) and Mineralocorticoid receptor antagonists (MRAs)) in accordance with applicable HF local/international guidelines and judgment of the investigator Further inclusion criteria apply.
Exclusion criteria:
1. 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
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 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) used simultaneously at Visit 2
* In case of acute decompensated HF:
* i.v. inotrope, i.v. vasodilating drug (e.g. nitrate, nitroprusside), or i.v. natriuretic peptide (e.g. nesiritide, carperitide), or mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device) within 24 hours prior to randomisation (Visit 2)
* i.v. diuretic with a dose that has been increased/intensified within 6 hours prior to randomisation (a stable dose of an i.v. diuretic is not exclusionary)
* Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2
* Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or planned during the trial
4. Myocardial infarction (MI), transient ischemic attack (TIA), stroke, coronary artery bypass graft (CABG) surgery, heart valve surgery/intervention or any other major surgery (major according to the investigator's assessment) within 90 days prior to Visit 2, or scheduled for major elective surgery (e.g. hip replacement, coronary artery bypass graft surgery/CABG)
5. Percutaneous coronary intervention (PCI) ( scheduled or unscheduled) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2
6. Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device (LVAD)
7. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or genetic hypertrophic cardiomyopathy,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
8. Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1 and until Visit 2
9. 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.
Primary outcome measure(s)
Time to first event of Cardiovascular (CV) death, hospitalisation for heart failure (HHF) or urgent heart failure (HF) visit — up to 42 months
Trial sites (653)
Facility
City
Region
Status
Diagnostic and Medical Clinic
Mobile
Alabama
Recruiting
Mobile Heart Specialists, PC
Mobile
Alabama
Recruiting
Velocity Clinical Research-Chula Vista
Chula Vista
California
Recruiting
University of California Irvine
Orange
California
Recruiting
North America Research Institute
San Dimas
California
Recruiting
Amicis Research Center - Valencia
Santa Clarita
California
Recruiting
Orange County Research Center
Tustin
California
Recruiting
Bridgeport Hospital
Bridgeport
Connecticut
Recruiting
Flourish Research
Boca Raton
Florida
Recruiting
Bay Area Cardiology
Brandon
Florida
Recruiting
Clearwater Cardiovascular and Interventional Consultants
Clearwater
Florida
Recruiting
Cardiology Associates Research Co.
Daytona Beach
Florida
Recruiting
Malcom Randall VA Medical Center
Gainesville
Florida
Recruiting
Velocity Clinical Research-Hallandale Beach-67888
Hallandale
Florida
Recruiting
University of Florida Health Jacksonville
Jacksonville
Florida
Recruiting
East Coast Institute for Research, LLC - Jacksonville
Jacksonville
Florida
Recruiting
First Coast Cardiovascular Institute
Jacksonville
Florida
Recruiting
Clearwater Cardiovascular Consultants-Largo-69917
Largo
Florida
Recruiting
University of Miami
Miami
Florida
Recruiting
Sacred Heart Medical Specialty Group
Miramar Beach
Florida
Recruiting
Advanced Research for Health Improvement, LLC
Naples
Florida
Not Yet Recruiting
Southwest Florida Research, LLC
Naples
Florida
Recruiting
Ocala Cardiovascular Research
Ocala
Florida
Recruiting
Ocala Research Institute, Inc
Ocala
Florida
Recruiting
Charlotte Cardiovascular Institute, PA
Port Charlotte
Florida
Recruiting
East Coast Institute for Research, LLC-Saint Augustine-63032
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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