Vicadrostat + Empagliflozin for Heart Failure

Recruiting at 347 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: MRAs, Potassium-sparing diuretics

Disqualifiers: Recent MI, Stroke, Heart transplant, 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: 1 to 3.5 years

4200 Participants Needed

Trial Summary

What is the purpose of this trial?

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 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 and empagliflozin tablets, and the other group takes placebo and 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 1 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. Participants also regularly answer questions about their well-being. The doctors document when participants experience worsening of their heart failure symptoms, must go to hospital due to heart failure, or die during the study. The time until these events are observed is compared between the treatment groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Will I have to stop taking my current medications?

You can continue your regular treatment for heart failure during the study, but you cannot take certain medications like mineralocorticoid receptor antagonists (e.g., spironolactone) or potassium-sparing diuretics within 14 days before starting the trial. Some other specific medications are also not allowed during the trial.

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

Empagliflozin has been shown to reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, regardless of whether they have diabetes. ^{1 2 3 4 5}

Is the combination of Vicadrostat and Empagliflozin safe for heart failure?

Empagliflozin is generally considered safe and well-tolerated, with benefits in heart failure and type 2 diabetes, but it can cause severe allergic reactions in some people. There is no specific safety data available for Vicadrostat in the provided research. ^{2 6 7 8 9}

What makes the drug combination of Vicadrostat and Empagliflozin unique for treating heart failure?

The combination of Vicadrostat and Empagliflozin for heart failure is unique because Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has shown benefits in reducing heart failure hospitalizations and mortality, even in patients without diabetes, by mechanisms not fully explained by its diuretic or blood sugar-lowering effects. This suggests a novel approach to heart failure treatment beyond traditional methods. ^{2 3 10 11 12}

Eligibility Criteria

Adults with chronic heart failure and a left ventricular ejection fraction (LVEF) under 40% can join this study. They must have been diagnosed at least 3 months prior. The trial excludes individuals based on specific criteria not provided here.

Inclusion Criteria

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

My heart failure treatment follows the best current guidelines.

I am at least 18 years old or the legal age of consent in my country.

Exclusion Criteria

Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device (LVAD)

I haven't taken an MRA in the last 14 days nor plan to during the trial.

I haven't taken potassium-sparing diuretics like amiloride in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vicadrostat and empagliflozin or placebo and empagliflozin for up to 3.5 years

1 to 3.5 years

Regular visits, exact number varies per participant

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin
• Vicadrostat

Trial Overview The trial is testing Vicadrostat combined with Empagliflozin versus a placebo paired with Empagliflozin to see if it helps those with chronic heart failure. Participants are randomly assigned to one of the two groups and will continue their regular heart failure treatments alongside the study drugs for up to about 3.5 years.

Participant Groups

Group I: vicadrostat + empagliflozin treatment group Experimental Treatment 2 Interventions

Group II: Placebo to vicadrostat + empagliflozin treatment group 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 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 a study of 3730 patients with heart failure and reduced ejection fraction, empagliflozin significantly reduced the combined risk of death, hospitalization for heart failure, and urgent heart failure visits, showing benefits as early as 12 days after starting treatment.

Empagliflozin also led to fewer hospitalizations requiring intensive care and reduced the need for diuretic intensification, while improving patients' functional class, demonstrating its efficacy in managing worsening heart failure events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. Packer, M., Anker, SD., Butler, J., 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]

A randomized controlled trial (RCT) showed that dapagliflozin significantly improves cardiovascular outcomes in heart failure patients, regardless of whether they have diabetes.

This suggests that dapagliflozin may be an effective treatment option for enhancing heart health in a broad range of heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribe an SGLT2 inhibitor for heart failure in the absence of diabetes? Koenigsberger, D., Marquez, A., Hughes, PR.[2022]

Empagliflozin is effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, which also leads to weight reduction and lower levels of glycated hemoglobin (HbA1C).

Beyond its use in diabetes, empagliflozin has shown significant benefits in heart failure treatment, reducing hospitalizations and cardiovascular deaths, while also providing nephroprotective effects, although it has some limitations and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Insights into the Use of Empagliflozin-A Comprehensive Review. Forycka, J., Hajdys, J., Krzemińska, J., et al.[2023]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

SGLT2 inhibitors (SGLT2i) showed a trend towards reducing the risk of cardiovascular death or heart failure hospitalization compared to sacubitril/valsartan and vericiguat, indicating their potential effectiveness in heart failure treatment.

SGLT2i demonstrated the greatest reduction in heart failure hospitalization rates compared to standard care and vericiguat, suggesting they may be the most effective therapy among the treatments analyzed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis. Aimo, A., Pateras, K., Stamatelopoulos, K., et al.[2022]

References

1. Poland pubmed.ncbi.nlm.nih.gov

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

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

Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Prescribe an SGLT2 inhibitor for heart failure in the absence of diabetes? [2022]

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

Effect of Dapagliflozin on Cause-Specific Mortality in Patients With Heart Failure Across the Spectrum of Ejection Fraction: A Participant-Level Pooled Analysis of DAPA-HF and DELIVER. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

After EMPA-REG OUTCOME and LEADER: Already a "New Era" in Therapy of Type 2 Diabetes? [2017]

7. Switzerland pubmed.ncbi.nlm.nih.gov

New Insights into the Use of Empagliflozin-A Comprehensive Review. [2023]

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

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Heart failure outcomes according to heart rate and effects of empagliflozin in patients of the EMPEROR-Preserved trial. [2023]

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

Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis. [2022]

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

Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart Failure. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. [2020]