BI 690517 + Empagliflozin for Heart Failure

Recruiting at 595 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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 and empagliflozin group: participants take vicadrostat 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 there is enough data to see if the treatment is working.

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.

What data supports the effectiveness of the drug empagliflozin for heart failure?

Empagliflozin has been shown to reduce the risk of cardiovascular death and hospitalization in adults with heart failure, even if they do not have diabetes, and it improves the quality of life for patients with chronic heart failure. ^{1 2 3 4 5}

Is the combination of BI 690517 and Empagliflozin safe for humans?

Empagliflozin (Jardiance) is generally considered safe and is approved for reducing the risk of heart-related issues in people with heart failure, even if they don't have diabetes. However, it is important to monitor for side effects like fluid loss. Safety data for BI 690517 specifically is not provided in the available research. ^{1 4 6 7 8}

What makes the drug BI 690517 + Empagliflozin unique for heart failure?

The combination of BI 690517 and Empagliflozin is unique because Empagliflozin, originally a diabetes medication, has been shown to reduce the risk of cardiovascular death and hospitalization in heart failure patients, regardless of their diabetes status, and across a wide range of heart function levels. ^{1 4 5 9 10}

Eligibility Criteria

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

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

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)

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

Trial Timeline

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

Treatment Details

Interventions

• BI 690517 (Other)
• Empagliflozin (Other)
• Placebo (Other)

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.

Participant Groups

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+

Findings from Research

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 (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]

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-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, 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. [2021]

3. Poland pubmed.ncbi.nlm.nih.gov

CLINICAL EFFECTIVENESS OF EMPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE. [2023]

4. England 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. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. Czech Republic pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

9. United States 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. [2023]

10. Belgium pubmed.ncbi.nlm.nih.gov

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