Empagliflozin for Heart Failure

(EMPA HF Trial)

Recruiting at1 trial location

Overseen by Jeffrey Testani, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Yale University

Must be taking: Loop diuretics

Must not be taking: Thiazide diuretics

Disqualifiers: Heart failure hospitalization, Renal therapy, Diabetes, Anemia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests empagliflozin in patients with worsening heart failure to see if it can help by removing extra sugar and salt from their bodies. The study includes patients with or without diabetes. Empagliflozin has been shown to reduce mortality and hospitalization for heart failure in diabetic patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it seems you can continue your current heart failure treatments, as the study involves adding empagliflozin or a placebo to your regimen.

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

Research shows that empagliflozin, a drug used for heart failure, can lower the risk of hospitalization and cardiovascular death in patients with different types of heart failure. Studies like the EMPEROR-Reduced and EMPEROR-Preserved trials have demonstrated its benefits in improving heart health outcomes. ^{1 2 3 4 5}

How is the drug empagliflozin unique for treating heart failure?

Empagliflozin is unique because it was originally developed for type 2 diabetes but is now approved to reduce the risk of death and hospitalization in heart failure patients, even those without diabetes. It works by helping the heart pump blood more effectively and is taken as a daily pill, making it a convenient option for managing chronic heart failure. ^{1 6 7 8 9}

Research Team

Jeffrey Testani, MD

Principal Investigator

Yale University

Eligibility Criteria

Adults over 18 with worsening heart failure, who've gained at least 5 lbs due to this condition and are on a stable dose of diuretics can join. They must have an eGFR ≥ 20 mL/min/1.73 m2 and be able to follow the study's procedures. Excluded are those with severe anemia, urinary issues, certain heart conditions, pregnant or breastfeeding women, or those needing hospitalization for heart failure.

Inclusion Criteria

I am 18 years old or older.

My doctor plans to adjust my water pill treatment for worsening heart failure.

I have been taking a water pill daily for at least a month.

Exclusion Criteria

Appears unlikely or unable to participate in the required study procedures, as assessed by the study PI, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease)

Inability to comply with the serial urine collection procedures

I have anemia with hemoglobin below 8g/dL or I am currently bleeding.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either empagliflozin or placebo for 6 weeks

6 weeks

Weekly visits (in-person)

Crossover Treatment

Participants initially on placebo switch to empagliflozin for an additional 6 weeks

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive empagliflozin to assess long-term effects

12 weeks

Treatment Details

Interventions

• Empagliflozin (Sodium-glucose cotransporter 2 (SGLT2) inhibitor)
• Placebo (Drug)

Trial Overview The trial is testing Empagliflozin (a diabetes medication) in patients with worsening heart failure regardless of their diabetes status. Participants will either receive Empagliflozin or a placebo for six weeks; then those on placebo will switch to the active drug for another six weeks.

Participant Groups

Group I: Placebo, Then Empagliflozin Experimental Treatment 2 Interventions

Participants first receive matching placebo daily for weeks 1-6, then will receive Empagliflozin 10 mg daily for weeks 7-12

Group II: Empagliflozin Experimental Treatment 1 Intervention

Empagliflozin 10 mg daily for weeks 1-6

Empagliflozin is already approved in Canada, Japan for the following indications:

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

Findings from Research

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]

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 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, 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 (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]

In the EMPEROR-Preserved study involving nearly 6000 participants, empagliflozin significantly reduced the risk of hospitalization for heart failure complications by about 30% after an average treatment duration of 26 months.

While side effects were generally similar between empagliflozin and placebo groups, there was a higher incidence of genital infections in those taking empagliflozin (2.2% vs. 0.7%), indicating a need for monitoring but overall suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin was beneficial in people with heart failure with preserved ejection fraction: plain language summary of the EMPEROR-Preserved study. Zannad, F., Macari, S.[2023]

References

1. 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]

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

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

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

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

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

Empagliflozin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Linagliptin and Metformin: A 24-Week Randomized, Double-Blind, Parallel-Group Trial. [2022]

5. 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]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Drug treatment with empagliflozin was beneficial in people with heart failure with preserved ejection fraction: plain language summary of the EMPEROR-Preserved study. [2023]