Empagliflozin for Heart Failure Risk

Overseen By Julie Dicken, RN

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Must not be taking: SGLT2 inhibitors, GLP1 agonists

Disqualifiers: Diabetes, Heart failure, Pregnancy, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how empagliflozin, a medication initially developed for type 2 diabetes, affects heart function in individuals at risk of heart failure. Participants will receive either the medication or a placebo to assess its impact on the heart's left atrium, which aids in pumping blood. It is ideal for those over 60 with high blood pressure and a body mass index of 30 or higher. The study aims to determine if empagliflozin could potentially prevent heart failure in people without diabetes. As an Early Phase 1 trial, this research focuses on understanding how empagliflozin works in people, offering participants a chance to contribute to groundbreaking medical insights.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain diabetes medications like SGLT2 inhibitors, GLP1 agonists, or DPP4 inhibitors. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that empagliflozin has been tested primarily in individuals with type 2 diabetes and heart issues. In one large study, participants who took empagliflozin had a lower risk of heart problems compared to those on a placebo. Another study found that empagliflozin helped individuals with heart failure by reducing their risk of heart and kidney problems.

Importantly, the FDA has already approved empagliflozin for treating type 2 diabetes, indicating its general safety. The studies reported no major safety concerns, which is reassuring. However, since this trial is in the early stages, researchers are still learning about its full safety for individuals at risk for heart failure. ^{1 2 3 4 5}

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

Researchers are excited about empagliflozin for heart failure because it offers a novel approach compared to traditional treatments. Unlike standard heart failure medications, which often focus on reducing blood pressure or enhancing heart contractility, empagliflozin is a type of SGLT2 inhibitor. This class of drugs was originally used to manage blood sugar levels in diabetes but has shown promise in heart failure by reducing hospitalizations and improving heart function. Its unique mechanism not only targets the kidneys to prevent glucose reabsorption but also has beneficial effects on heart and kidney health, making it a promising option for heart failure management.

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

This trial will evaluate empagliflozin's effectiveness in reducing heart failure risk. Studies have shown that empagliflozin can be highly effective for heart issues. In individuals with type 2 diabetes, it has lowered the risk of heart-related problems by about 25% to 35%. It also reduces the likelihood of hospitalization due to heart failure. This treatment works by blocking a protein in the kidneys, which helps lower blood sugar and benefits the heart. Some research even shows a 21% reduction in the risk of heart failure or death from heart-related causes. Overall, empagliflozin shows promise for those at risk of heart failure. Participants in this trial will join either the experimental group receiving empagliflozin or a placebo group for comparison. ^{4 6 7 8 9}

Who Is on the Research Team?

Jeremy Van't Hof, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults over 60 with high blood pressure and a BMI of at least 30kg/m2, who may be at risk for heart failure. They must have had an echocardiogram within the last 60 days. It's not specified who can't join, but typically those with conditions that could interfere with the study or their safety would be excluded.

Inclusion Criteria

Body mass index ≥30kg/m2

Participants with an echocardiogram within 60 days of the baseline visit

I have been diagnosed with high blood pressure.

Exclusion Criteria

I have had infections in my urinary or genital area before.

I haven't had, nor am I scheduled for, major surgery around the time of my first visit.

Non-English speaking individuals

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 10mg empagliflozin or placebo daily to assess the effect on left atrial function

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The trial is testing empagliflozin, a drug initially used for type 2 diabetes, to see if it improves left atrial function in patients at risk of developing heart failure. Participants will either receive empagliflozin or a placebo without knowing which one they're taking (double-blinded).

How Is the Trial Designed?

Group I: Experimental group Experimental Treatment 1 Intervention

Group II: Placebo group Placebo Group 1 Intervention

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?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

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]

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 (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]

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 (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 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40955256/

Empagliflozin and Cardiovascular Outcomes: A Systematic ... The safety profile of empagliflozin was favorable, with the main adverse event being an increased incidence of mild genital infections, and no ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1504720

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069217

Effect of Empagliflozin on Heart Failure Outcomes After ... Empagliflozin reduced the risk of first and total heart failure (HF) hospitalizations by 23% and 33%, respectively, in patients with left ...

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

Efficacy of Empagliflozin in Patients With Heart Failure ... Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: ...

5. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/landmark-trial-demonstrates-jardiance-empagliflozin-first-therapy-show-statistically-significant

Jardiance® (empagliflozin) Shows Improvement in Heart ... This first for adults with heart failure shows an impressive 21% risk reduction in patients at risk of CV death or hospitalization if using ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12433617/

Empagliflozin and Cardiovascular Outcomes: A Systematic ... Empagliflozin was consistently associated with significant reductions in major adverse cardiovascular events, notably a 14-38% reduction in ...

8. 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 ...

9. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/results-announced-empact-mi-phase-iii-trial

Results announced from EMPACT-MI phase III trial Additional pre-specified exploratory analyses revealed relative risk reductions of 23% for time to first hospitalization due to heart failure ...