Finerenone + Empagliflozin for Heart Failure

(CONFIRMATION Trial)

Recruiting at 18 trial locations

Overseen By Marc Bonaca

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Colorado Prevention Center

Must not be taking: MRA, SGLT2i, CYP3A4 inhibitors

Disqualifiers: Type 1 diabetes, Severe hyperkalemia, eGFR <30, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 6 months

1500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two drugs, finerenone and empagliflozin, works better than usual care for people with heart failure. The researchers will assess whether these drugs, taken together, are safe and effective in treating heart failure symptoms during or immediately after a hospital stay. Individuals recently hospitalized for heart failure and still experiencing symptoms might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking non-steroidal mineralocorticoid receptor antagonists (MRA) or SGLT2 inhibitors. If you are on these medications, you will need to discontinue them to participate in the study.

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

Research has shown that the combination of finerenone and empagliflozin is generally well-tolerated. Studies have found that using these two drugs together can significantly improve heart and kidney health. Earlier research indicated that this combination reduced a specific protein in urine, a positive sign for kidney health.

Some side effects require attention. Finerenone can alter kidney function, as studies observed a temporary decrease in the kidney's filtering ability. However, this change was not significant over time and did not cause serious problems. Empagliflozin, which supports heart and kidney health, has also proven safe for many patients.

Overall, these drugs have demonstrated positive safety results in previous research, and their combination has been studied for its benefits and safety. Always consult a healthcare provider with any concerns or questions about joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of finerenone and empagliflozin for heart failure because these drugs offer distinct mechanisms of action that could enhance treatment effectiveness. Finerenone is a non-steroidal mineralocorticoid receptor antagonist that targets inflammation and fibrosis in heart tissues, potentially reducing heart damage. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, primarily used for diabetes, has shown benefits in reducing cardiovascular events by improving heart function and reducing fluid overload. Together, these treatments might provide a more comprehensive approach to managing heart failure, addressing multiple pathways that contribute to the condition.

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

Research shows that both finerenone and empagliflozin can improve heart health. Finerenone has lowered hospital visits due to heart failure and increased the lifespan of people with type 2 diabetes. Empagliflozin, an SGLT2 inhibitor, also reduces heart-related problems in similar patients. In this trial, participants will receive either the combination of finerenone and empagliflozin or usual care. Together, these treatments aim to boost heart and kidney function, offering hope for those with heart failure. Studies suggest that this combination could lead to better results than standard care alone. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults hospitalized with heart failure who have certain levels of heart stress markers (NTproBNP or BNP) and received IV diuretics can join. They must consent to the study, not be pregnant, agree to use contraception if applicable, and meet stabilization criteria.

Inclusion Criteria

My heart stress test levels are higher than normal.

I received an IV dose of a water pill during my hospital stay.

Fulfillment of protocol defined stabilization criteria (if randomized during hospitalization)

Exclusion Criteria

I am currently taking medication for heart or kidney health.

My kidney function is low or my potassium levels are high.

I have type 1 diabetes or have had diabetic ketoacidosis before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with finerenone and empagliflozin compared to usual care

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Finerenone

Trial Overview The trial is testing a combination of two drugs, Finerenone and Empagliflozin, against usual care in patients with heart failure to see which is more effective and safe.

How Is the Trial Designed?

Group I: Finerenone plus empagliflozin Experimental Treatment 2 Interventions

Group II: Usual care Active Control 1 Intervention

Usual care management

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Colorado Prevention Center

Lead Sponsor

Trials

13

Recruited

22,600+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Saint Luke's Hospital of Kansas City

Collaborator

Trials

4

Recruited

10,600+

Saint Luke's Mid America Heart Institute

Collaborator

Trials

3

Recruited

1,900+

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Industry Sponsor

Trials

28

Recruited

126,000+

St. Luke's Hospital, Kansas City, Missouri

Collaborator

Trials

9

Recruited

12,500+

Published Research Related to This Trial

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 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 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]

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 (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 (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 (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9797657/

Comparison the effects of finerenone and SGLT2i on ... Finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes ...

2. diabetesjournals.org diabetesjournals.org/care/article/48/5/745/157943/Efficacy-and-Safety-of-Finerenone-in-Type-2

Efficacy and Safety of Finerenone in Type 2 Diabetes Finerenone consistently reduced the kidney composite outcome, HF hospitalization, major adverse cardiovascular events, and all-cause mortality, ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2110956

Cardiovascular Events with Finerenone in Kidney Disease ... In the FIGARO-DKD trial, finerenone therapy improved cardiovascular outcomes, as compared with placebo, in patients with type 2 diabetes who had ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0735109724102525

Finerenone and Kidney Outcomes in Patients With Heart ... Finerenone led to a greater reduction in initial eGFR, but did not result in a significant difference in chronic eGFR slope, vs. placebo.

5. jacc.org jacc.org/doi/10.1016/j.jchf.2025.03.006

Finerenone Across the Spectrum of Kidney Risk in Heart ... Finerenone appears to consistently improve clinical outcomes, HF-related health status, and albuminuria across a broad spectrum of kidney risk in patients with ...

6. jacc.org jacc.org/doi/10.1016/j.jacc.2024.10.091

Finerenone and Kidney Outcomes in Patients With Heart ... Finerenone led to a greater reduction in initial eGFR, but did not result in a significant difference in chronic eGFR slope, vs. placebo.

7. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/kerendia-jardiance-combination-ckd-t2d

CONFIDENCE Trial Demonstrates Superior Outcomes With ... Simultaneous initiation of Kerendia (finerenone) and Jardiance (empagliflozin) led to a 52% reduction in urine albumin-to-creatinine ratio (UACR) ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/215341Orig1s000IntegratedR.pdf

215341Orig1s000 - accessdata.fda.gov ... Safety and Tolerability of. Different Oral Doses of BAY 94-8862 in Subjects With Stable Chronic Heart Failure With. Left Ventricular Systolic ...