Evaluation of Vicadrostat (BI 690517) and Empagliflozin Efficacy and Safety in Patients with Symptomatic Chronic Heart Failure and Reduced Ejection Fraction
- Trial ID
- 2024-519525-38-00
- Protocol
- 1378-0018
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **superiority** of the combination of vicadrostat and empagliflozin compared with placebo and empagliflozin for the time to first event of cardiovascular (CV) death, hospitalization for heart failure (HHF), or urgent heart failure (HF) visit in participants with heart failure and left ventricular ejection fraction (LVEF) less than 40% who are not taking mineralocorticoid receptor antagonists (MRA). This is clinically relevant as it aims to improve outcomes in patients with symptomatic chronic heart failure, a condition associated with high morbidity and mortality.
Secondary objectives include:
- Demonstrating the superiority of the combination for the time to first event of CV death or HHF, the total number of HHF (first and recurrent), the absolute change from baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) at Week 32, the time to CV death, and the time to all-cause mortality.
- Evaluating the combination for the time to first HHF, time to first occurrence of the composite renal endpoint, and the absolute change from baseline in KCCQ Clinical Summary Score (KCCQ-CSS) at Week 32, in KCCQ-TSS at Week 52, and in KCCQ Overall Summary Score (KCCQ-OSS) at Week 32 and 52. Additionally, assessing the absolute change from baseline in systolic blood pressure (SBP) at Week 32 in participants with baseline SBP ≥ 130 mmHg and in diastolic blood pressure (DBP) at Week 32 in participants with baseline DBP ≥ 80 mmHg.
Participants
The clinical trial involves a total of **2661 participants** diagnosed with **heart failure**. The study population includes both male and female subjects, aged 18 years and older, with no specific upper age limit mentioned. Participants are required to have a left ventricular ejection fraction (LVEF) of less than 40% and must not be taking mineralocorticoid receptor antagonists (MRA). The trial population was selected based on specific inclusion criteria, including a diagnosis of chronic heart failure for at least three months prior to the study and classification within New York Heart Association (NYHA) classes II to IV. Participants must have elevated NT-proBNP levels and be treated according to the best possible standard of care, excluding SGLT2 inhibitors and MRA. The study does not include a vulnerable population, and lifestyle factors such as diet and physical activity are not specified. The selection process ensures that participants are receiving appropriate heart failure management, including the use of ACE inhibitors, ARBs, or ARNis, and beta-blockers, as deemed suitable by their treating physician.
Plans and Procedures
The clinical trial is a **Phase III**, double-blind, randomized, parallel-group superiority study designed to evaluate the efficacy and safety of the combined use of oral vicadrostat (BI 690517) and empagliflozin compared with placebo and empagliflozin in participants with symptomatic **chronic heart failure** and left ventricular ejection fraction (LVEF) less than 40%. The trial aims to demonstrate the superiority of the combination therapy for the time to first event of cardiovascular death, hospitalization for heart failure, or urgent heart failure visit in participants not taking mineralocorticoid receptor antagonists (MRA). The trial is expected to commence recruitment on November 4, 2025, and conclude by January 20, 2028.
Participants will be involved in the study for a maximum treatment period of 43 weeks. The trial will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, informed consent, and specific heart failure parameters; a randomization visit where participants will be assigned to either the treatment or placebo group; and multiple follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will assess the primary and secondary endpoints, including time to first event of cardiovascular death or hospitalization for heart failure, occurrences of hospitalization for heart failure, and changes in the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score at Week 32.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial will adhere to the highest standards of clinical research, ensuring that all procedures are conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines and local regulations.
Treatment
The clinical trial involves the administration of **BI 690517**, an experimental medication, in the form of a **film-coated tablet**. The active substance, also named BI 690517, is of chemical origin. The medication is administered orally. The trial protocol specifies a maximum treatment period of 43 days. The dosage and frequency of administration are determined by the study protocol, although specific dosing details are not provided in the available data. Participant compliance with the dosing regimen is monitored throughout the study period.
**Empagliflozin** is used as a non-experimental treatment in this study. It is also provided in the form of a film-coated tablet and is administered orally. Empagliflozin serves as a standard-of-care therapy in combination with the experimental treatment. The maximum treatment period for empagliflozin is also 43 days, aligning with the experimental medication's schedule. The specific dosage and frequency of administration are not detailed in the provided data.
A **placebo** matching vicadrostat is utilized as a comparator treatment in the trial. The placebo is designed to mimic the appearance of the experimental medication to maintain blinding. The pharmaceutical form, dosage, and route of administration for the placebo are not specified in the available data. The placebo is administered in a manner consistent with the experimental treatment to ensure the integrity of the study design.
Efficacy
The efficacy of the clinical trial will be assessed through a composite primary endpoint, which includes the time to the first event of **cardiovascular (CV) death**, hospitalization for heart failure (HHF), or an urgent heart failure (HF) visit. This endpoint is designed to evaluate the primary objective of demonstrating the superiority of the combination of vicadrostat and empagliflozin compared to placebo and empagliflozin in participants with symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF) of less than 40%.
Secondary endpoints will include the time to the first event of cardiovascular death or hospitalization for heart failure, occurrences of hospitalization for heart failure (both first and recurrent), and the absolute change from baseline in the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 32. These endpoints will provide additional insights into the efficacy of the treatment regimen.
The efficacy parameters will be measured and collected at specified timepoints throughout the trial, with the KCCQ-TSS being assessed at Week 32. The analysis of these parameters will be conducted using validated scales and laboratory tests to ensure the accuracy and reliability of the results. The trial is structured as a Phase III double-blind, randomized, parallel-group superiority trial, with an estimated end date of January 20, 2028, and a recruitment start date of November 4, 2025.
Inclusion and Exclusion Criteria
Inclusion Criteria
- At least 18 years old and at least at 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 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 Section 4.2.2.3 of the protocol
- Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA classes II to 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 randomisation at Visit 2 (if several LVEF assessments are available, the most recent one should be considered)
- Elevated NT-proBNP at Visit 1, analysed at the central laboratory: a. ≥ 600 pg/mL (or ≥ 400 pg/mL if hospitalised for HF within the previous 12 months,) for participants without Afib or Aflutter (Visit 1 ECG2) or b. ≥ 1200 pg/mL for participants with Afib or Aflutter (Visit 1 ECG2) (irrespective of history of HHF)
- Treated according to best possible SOC (disregarding SGLT2i and MRA) in accordance with applicable HF local/international guidelines and judgement of the investigator, which should in general include (unless contraindicated or not tolerated): • An ACE inhibitor, or ARB or ARNi; and • A beta-blocker; and • If considered appropriate by the patient’s treating physician, an SGLT2i (prior SGLT2i treatment will be replaced by the study drug at randomisation)
Exclusion Criteria
- 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 an MRA should not be discontinued with the intention of study enrolment.
- 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 ACEi, ARB or ARNi used simultaneously at Visit 2 • Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or planned during the trial • Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2 • In case of acute decompensated HF: o 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 o 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)
- MI, TIA, stroke, coronary artery bypass graft surgery (CABG), 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, CABG)
- Percutaneous coronary intervention (PCI) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2
- Heart transplant recipient, awaiting heart transplant, or currently implanted 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 12 months prior to Visit 1 and until Visit 2
- Acute inflammatory heart disease, such as acute myocarditis, within 90 days preceding prior to Visit 1 and until Visit 2
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 04 Nov 2025 | 9 |
 Bulgaria | Recruiting | 04 Nov 2025 | 701 |
 Czechia | Recruiting | 04 Nov 2025 | 105 |
 Denmark | Recruiting | 04 Nov 2025 | 35 |
 Germany | Recruiting | 04 Nov 2025 | 210 |
 Hungary | Recruiting | 04 Nov 2025 | 104 |
 Italy | Recruiting | 04 Nov 2025 | 23 |
 The Netherlands | Recruiting | 04 Nov 2025 | — |
 Poland | Recruiting | 04 Nov 2025 | 181 |
 Romania | Recruiting | 04 Nov 2025 | 69 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BI 690517 | Test | FILM COATED TABLET | ORAL | 00 | 43 | PRD11187391 |
EMPAGLIFLOZIN | Test | — | ORAL | 00 | 43 | SUB35915 |
Placebo matching vicadrostat | Placebo | N/A | — | — | — | N/A |