Heart Failure
Conditions
Brief summary
This study is open to adults with chronic heart failure (HF) who have a reduced left ventricular ejection fraction (LVEF) of less than 40%. People can join the study if they have been diagnosed with chronic HF at least 3 months before they start on the study. The purpose of this study is to find out whether a medicine called vicadrostat, in combination with another medicine called empagliflozin, helps people with chronic heart failure. In this study, participants are put into 2 groups randomly. Participants have an equal chance of being in either group. One group takes vicadrostat/empagliflozin tablets, and the other group takes placebo/empagliflozin tablets. Placebo tablets look like vicadrostat tablets but do not contain any medicine. Participants take the study medicines as tablets once a day for between about 6 months and about 3.5 years. During this time, they can continue their regular treatment for heart failure. Participants can stay in the study as long as they benefit from treatment and can tolerate it, for a maximum of about 3.5 years. During this time, they visit the study site regularly. The exact number of visits is different for each participant, depending on how long they stay in the study. The study staff may also contact the participants by phone for some visits. Participants also regularly answer questions about their well-being. The doctors document when participants experience worsening of their heart failure symptoms, go to hospital due to heart failure or die during the study. The time until these events are observed is compared between the two treatment groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years old and at least at the legal age of consent in countries where it is greater than 18 years 2. Signed and dated written informed consent in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (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 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 protocol. 4. Chronic heart failure (HF) diagnosed at least 3 months before Visit 1, and in New York Heart Association (NYHA) classes II to IV at Visit 1, with left ventricular ejection fraction (LVEF) \< 40% per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, magnetic resonance imaging (MRI), or computed tomography (CT)). 5. Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysed at the central laboratory 6. Treated according to best possible standard of care (SOC) (disregarding sodium-dependent glucose co-transporter 2 inhibitor (SGLT2i) and mineralocorticoid receptor antagonist (MRA)) in accordance with applicable heart failure (HF) local/international guidelines and judgement of the investigator. Additional inclusion criteria apply.
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 an MRA should not be discontinued with the intention of study enrolment. 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 * 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: * 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 * 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) 4. Myocardial infarction (MI), transient ischemic attack (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) 5. Percutaneous coronary intervention (PCI) 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 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 8. Acute inflammatory heart disease, such as acute myocarditis, within 90 days preceding prior to Visit 1 and until Visit 2 Further
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first event of Cardiovascular (CV) death, or Hospitalisation for heart failure (HHF), or Urgent heart failure (HF) visit | up to 43 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key secondary endpoint: Time to first event of cardiovascular death or HHF | up to 43 months | — |
| Key secondary endpoint: Occurrences of HHF (first and recurrent) | up to 43 months | — |
| Key secondary endpoint: Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 32 | at baseline, at week 32 | The KCCQ is a participant reported outcome. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in people with heart failure. The symptom frequency and symptom burden domains are merged into a total symptom score (TSS). Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
| Key secondary endpoint: Time to cardiovascular death | up to 43 months | — |
| Key secondary endpoint: Time to all-cause mortality | up to 43 months | — |
| Time to first HHF | up to 43 months | — |
| Time to first occurrence of death from kidney failure, chronic dialysis* or renal transplant or onset of sustained reduction of ≥ 50% estimated glomerular filtration rate (eGFR) or onset of sustained eGFR (CKD-EPI)cr < 10 mL/min/1.73 m² | from baseline, up to 43 months | \* Chronic dialysis is defined as dialysis continuing for at least 30 days. For this composite renal endpoint the Chronic Kidney Disease Epidemiology Collaboration creatinine ((CKD-EPI)cr) equation is used. |
| Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire- Clinical Summary Score (KCCQ-CSS) at Week 32 | at baseline, at week 32 | The KCCQ is a participant reported outcome. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in people with heart failure. The Clinical Summary Score (CSS) of the KCCQ provides a measure of symptoms and physical limitations associated with heart failure. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
| Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 52 | at baseline, at week 52 | The KCCQ is a participant reported outcome. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in people with heart failure. The symptom frequency and symptom burden domains are merged into a total symptom score (TSS). Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
| Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire- Overall Summary Score (KCCQ-OSS) at Week 32 | at baseline, at week 32 | The KCCQ is a participant reported outcome. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in people with heart failure. In the KCCQ, an overall summary score (OSS) can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
| Absolute change from baseline in KCCQ-OSS at Week 52 | at baseline, at week 52 | The KCCQ is a participant reported outcome. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in people with heart failure. In the KCCQ, an overall summary score (OSS) can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
| Absolute change from baseline in systolic blood pressure (SBP) [mmHg] at Week 32 in participants with baseline SBP ≥ 130 mmHg | at baseline, at week 32 | — |
| Absolute change from baseline in diastolic blood pressure (DBP) [mmHg] at Week 32 in participants with baseline DBP ≥ 80 mmHg | at baseline, at week 32 | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Poland, Romania, Saudi Arabia, Serbia, Slovakia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTBoehringer Ingelheim
Outcome results
None listed