Empagliflozin for Heart Failure

(EMPA HF Trial)

Recruiting at 1 trial location

Overseen By Kara Otis

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well empagliflozin works for individuals with worsening heart failure, regardless of diabetes status. Researchers are comparing empagliflozin, a medication for heart failure, to a placebo (a pill with no active drug) to assess its effects over 6 weeks. After this period, participants on the placebo will switch to empagliflozin for another 6 weeks. Suitable candidates have worsening heart failure, are already taking certain diuretics, and have recently gained at least 5 pounds. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

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

Research has shown that empagliflozin is generally safe for people with heart failure. One study found it lowered the risk of hospitalization for heart failure or death from heart-related issues by 34%. Another study reported an 8% reduction in the risk of death from heart problems compared to a placebo. These findings suggest that empagliflozin is safe for people with heart conditions. While side effects can occur with any treatment, evidence indicates that empagliflozin effectively improves heart health without major safety concerns. ^{1 2 3 4 5}

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

Empagliflozin is unique because it targets heart failure by reducing excess fluid in the body through a mechanism known as SGLT2 inhibition. Unlike standard treatments like ACE inhibitors or beta-blockers that focus on heart rate and blood pressure, empagliflozin helps the kidneys remove sugar and water, reducing the strain on the heart. Researchers are excited because it offers an innovative way to address heart failure symptoms and could improve patient outcomes by offering a different pathway to manage the condition. Plus, its dual role in managing blood sugar and heart failure makes it particularly appealing for patients with coexisting diabetes.

What evidence suggests that empagliflozin might be an effective treatment for heart failure?

Research has shown that empagliflozin effectively treats heart failure. Studies have found it can lower the risk of hospitalization for heart failure or death from heart-related issues by 34%. This significantly reduces the chances of serious heart problems. Empagliflozin benefits patients with both types of heart failure: those with reduced heart pumping ability and those with normal pumping function. In this trial, participants will either receive empagliflozin directly or start with a placebo before switching to empagliflozin. These findings suggest that empagliflozin can help people with heart failure manage their condition more effectively. ^{1 4 6 7 8}

Who Is on the Research Team?

Jeffrey Testani, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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

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.

I have gained at least 5 lbs recently.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Placebo

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.

How Is the Trial Designed?

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 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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

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]

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]

In a study involving 333 patients with type 2 diabetes, empagliflozin significantly reduced HbA1c levels compared to placebo after 24 weeks, indicating improved glycemic control when used alongside linagliptin and metformin.

Empagliflozin also led to significant reductions in fasting plasma glucose and body weight, and it was well tolerated, with fewer adverse events reported compared to the placebo group.

NCBI (Pubmed)

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. Søfteland, E., Meier, JJ., Vangen, B., et al.[2022]

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107038

Empagliflozin in Heart Failure with a Preserved Ejection ... Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4872285/

Heart failure outcomes with empagliflozin in patients ... In this trial, empagliflozin reduced the risk of hospitalization for heart failure or cardiovascular death by 34%, corresponding to a number needed to treat ...

3. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/hfpef-disease/efficacy

HFpEF Efficacy & Data | Jardiance® (empagliflozin) tablets JARDIANCE reduced the number of worsening HF events · In a secondary analysis of the EMPEROR-Preserved trial, JARDIANCE improved time to worsening HF events, ...

4. jacc.org jacc.org/doi/10.1016/j.jacc.2023.03.390

Efficacy of Empagliflozin in Patients With Heart Failure ... Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36342696/

Cost-effectiveness of Empagliflozin in Patients With ... - PubMed The long-term cost-effectiveness of empagliflozin among patients who have heart failure with preserved ejection fraction (HFpEF) remains unclear ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2022190

Cardiovascular and Renal Outcomes with Empagliflozin in ... The risk of cardiovascular death was 8% lower with empagliflozin than with placebo in our trial (hazard ratio, 0.92; 95% CI, 0.75 to 1.12) and ...

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.027652

Impact of Empagliflozin in Heart Failure With Reduced ... Second, empagliflozin reduced the risk of primary composite outcome, its components, and composite renal outcomes in patients with HF ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1262363622000994

Empagliflozin cardiovascular and renal effectiveness and ... In EMRPISE US studies, initiation of empagliflozin was associated with a lower risk of hospitalization for heart failure (HHF), all-cause mortality (ACM), and a ...