BI 690517 + Empagliflozin for Heart Failure

Recruiting at 800 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must be taking: Diuretics

Must not be taking: MRAs, Potassium-sparing diuretics

Disqualifiers: Heart transplant, Cardiomyopathy, Severe valvular disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

6000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new combination of medications, BI 690517 (an experimental treatment) and empagliflozin, can improve symptoms and heart function in people with heart failure. Participants will be randomly assigned to receive either the actual medications or a placebo (a pill with no active ingredients) along with empagliflozin. The trial seeks individuals diagnosed with heart failure for at least three months who experience symptoms affecting daily life, such as fatigue or shortness of breath. Participants will regularly visit doctors for health check-ups and report their symptoms to help researchers understand the treatment's effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like mineralocorticoid receptor antagonists or potassium-sparing diuretics before joining. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining vicadrostat (BI 690517) and empagliflozin is being tested to help people with heart failure. In earlier studies, these drugs were used separately and were generally well-tolerated.

Empagliflozin, for instance, has FDA approval for treating diabetes and has been safely used by many patients, indicating its safety for diabetes management.

Vicadrostat remains under study, but early results from other heart failure research suggest it may be safe when used with empagliflozin. Participants in those studies did not report many serious side effects.

As the trial progresses, evidence suggests the treatment is generally safe for people. However, each person's experience can differ. Regular check-ups during the study monitor any unwanted effects and ensure safety as much as possible. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Researchers are excited about the combination of BI 690517 and Empagliflozin for heart failure because this treatment approach offers a novel mechanism of action compared to current options. While standard treatments for heart failure, such as ACE inhibitors and beta-blockers, primarily focus on managing symptoms and reducing strain on the heart, BI 690517 targets a new pathway that could enhance heart function more directly. Additionally, Empagliflozin, a well-known SGLT2 inhibitor, has shown promise in improving outcomes for patients with heart failure by reducing fluid overload and improving cardiovascular health. The combination of these two drugs could provide a more comprehensive and effective solution for managing heart failure, which is why researchers are eager to explore its potential.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will evaluate the combination of vicadrostat (BI 690517) with empagliflozin for heart failure. Research has shown that vicadrostat blocks certain hormones that can harm the heart and kidneys. Studies suggest that when combined with empagliflozin, it may enhance heart and kidney health. Empagliflozin is already known to help people with heart failure by reducing the risk of heart problems. Together, these treatments aim to improve overall heart and kidney function, offering hope for those with heart failure. Participants in this trial may receive either the combination of vicadrostat and empagliflozin or a placebo with empagliflozin. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults with heart failure, having symptoms and a left ventricular ejection fraction of 40% or higher can join. They must be on stable diuretic therapy, have been hospitalized for heart failure within the last 6 months, and fit specific criteria based on body mass index and presence of atrial fibrillation or flutter.

Inclusion Criteria

Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysed at the central laboratory at Visit 1

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)

I have signed and understand the consent form for this trial.

Exclusion Criteria

I haven't taken drugs like spironolactone or eplerenone in the last 14 days.

I haven't taken amiloride or similar water pills in the last 14 days.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either vicadrostat and empagliflozin or placebo and empagliflozin as tablets once a day. Regular health checks and monitoring for unwanted effects are conducted.

32 weeks

Regular visits (in-person), additional contacts by phone

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term monitoring

Participants continue to be monitored for long-term outcomes such as kidney function and overall health status.

Up to 42 months

What Are the Treatments Tested in This Trial?

Interventions

• BI 690517
• Empagliflozin
• Placebo

Trial Overview The trial is testing BI 690517 combined with empagliflozin against a placebo combined with empagliflozin in people with heart failure. Participants are randomly assigned to one of these two groups and take the tablets daily while their health is monitored over time.

How Is the Trial Designed?

Group I: vicadrostat/empagliflozin Experimental Treatment 2 Interventions

Group II: placebo/empagliflozin Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

Empagliflozin, originally developed for type 2 diabetes, has been shown to significantly reduce the risk of cardiovascular death and hospitalization for heart failure in patients with symptomatic chronic heart failure, regardless of their left ventricular ejection fraction, based on pivotal phase III trials.

The treatment not only improved cardiovascular outcomes but also enhanced health-related quality of life and was well tolerated, with a safety profile similar to that observed in diabetes patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin: A Review in Symptomatic Chronic Heart Failure. Frampton, JE.[2022]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. Chen, G., Zhang, D., Du, A., et al.[2021]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

Empagliflozin has been shown to improve cardiorenal outcomes and reduce hospitalization risk for heart failure in patients with diabetes, as demonstrated in the EMPA-REG OUTCOME study.

Clinical studies (EMPEROR-Preserved, EMPEROR-Reduced, EMPULSE) indicate that empagliflozin provides significant benefits over traditional heart failure therapies, including reduced mortality and hospitalizations, and improved quality of life for patients with various heart failure phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLINICAL EFFECTIVENESS OF EMPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE. Rоsul, ММ., Bletskan, ММ., Ivano, NV., et al.[2023]

In the EMPEROR-Preserved trial, empagliflozin significantly reduced the risk of cardiovascular death or hospitalization for heart failure in patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) by 17% compared to placebo, involving 4,005 participants.

For patients with mid-range LVEF (41-49%), empagliflozin showed an even greater reduction in risk for the same outcomes, with a hazard ratio of 0.71, indicating strong efficacy across different LVEF categories in heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved. Anker, SD., Butler, J., Usman, MS., et al.[2023]

Empagliflozin (EMPA) significantly reduced the induction of ventricular fibrillation (VF) in an ex-vivo model of ischemia-reperfusion, with only 16.7% of EMPA-treated hearts experiencing VF compared to 60% in control hearts.

EMPA improved cardiac contractility, as shown by a higher left ventricular developed pressure (LVDP) and enhanced calcium cycling, indicating its potential to protect heart function during ischemic events through mechanisms that do not involve sodium-glucose co-transporter-2 (SGLT2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. Azam, MA., Chakraborty, P., Si, D., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06935370

NCT06935370 | A Study to Test Whether Vicadrostat (BI ... This study is open to adults with chronic heart failure (HF) who have a reduced left ventricular ejection fraction (LVEF) of less than 40%.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39533115/

a rationale for the EASi-KIDNEY trial The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a ...

3. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/heart-diseases/heart-failure/easi-hf-phase-iii-trial-patients-hfpef

EASi-HF™ Phase III trial in patients with HFpEF There is potential for vicadrostat with empagliflozin to improve overall cardiovascular, renal and metabolic health, as positive outcomes in one condition ...

4. prohealthcare.org prohealthcare.org/medical-services/clinical-trials/details/?id=199

EASi-HF - Clinical Trials Details 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 ...

5. trialx.com trialx.com/clinical-trials/listings/293557/a-study-to-test-whether-bi-690517-in-combination-with-empagliflozin-helps-people-with-heart-failure/?&radius=10&place=Seoul,%20etc.&user_country=Korea,%20Republic%20of

A Study to Test Whether Vicadrostat in Combination With ... The purpose of this study is to find out whether vicadrostat (BI 690517) in combination with empagliflozin helps people with heart failure.

6. boehringer-ingelheim.com boehringer-ingelheim.com/science-innovation/human-health-innovation/clinical-pipeline/vicadrostat-bi-690517-empagliflozin-0

Vicadrostat (BI 690517) / empagliflozin The purpose of the EASi-HF® Preserved trial is to find out whether vicadrostat/empagliflozin helps people with heart failure with preserved ejection fraction.