Empagliflozin for Congenital Heart Disease

(EMPA-HEART-3 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Subodh Verma

Must not be taking: SGLT2 inhibitors

Disqualifiers: Pregnancy, Type 1 diabetes, 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: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether empagliflozin can aid individuals with Fontan Circulatory Failure (FCF), a condition where the heart struggles to pump blood effectively after specific heart surgery for a birth defect. The goal is to determine if this medication can enhance the quality of life for those affected. Participants will receive either empagliflozin or a placebo (a sugar pill with no active ingredients) to compare results. The trial is suitable for adults who have difficulty with daily activities due to FCF and are not currently on certain heart medications or dealing with other significant health issues. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot join if you recently started or changed the dose of a diuretic or if you are currently on an SGLT2 inhibitor or have been in the last 12 weeks.

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

Previous studies have shown that empagliflozin is generally safe and well-tolerated for patients with heart conditions. Research indicates that empagliflozin, an SGLT2 inhibitor, is well-tolerated in individuals with congenital heart disease. These studies have not identified any major safety concerns.

Common safety measures, such as blood pressure and kidney function, remained stable when patients began taking this medication. Empagliflozin even improved heart health and reduced the risk of heart failure symptoms. While all medications can have side effects, available evidence suggests empagliflozin is a safe option for many with heart conditions. ^{1 2 3 4 5}

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

Unlike the standard treatments for congenital heart disease, which often focus on surgical interventions and medications to manage symptoms, Empagliflozin offers a different approach by targeting glucose metabolism. This drug, originally used for type 2 diabetes, works by inhibiting the sodium-glucose co-transporter 2 (SGLT2) in the kidneys, which helps reduce heart stress by lowering blood glucose levels and potentially improving heart function. Researchers are excited about Empagliflozin because it presents a novel mechanism of action that could offer additional cardiovascular benefits beyond traditional therapies.

What evidence suggests that empagliflozin might be an effective treatment for Fontan Circulatory Failure?

Research has shown that empagliflozin, which participants in this trial may receive, can reduce hospital visits and deaths related to heart problems in individuals with heart issues. Other studies have found that empagliflozin improves heart function and overall well-being compared to other treatments. This drug belongs to a group called SGLT2 inhibitors, which are generally safe and can significantly lower the risk of heart failure in people with complex heart conditions. These findings suggest that empagliflozin could help manage heart problems for those with only one working heart ventricle, possibly delaying the need for a heart transplant. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with a congenital heart defect where only one ventricle functions, managed by Fontan operation but now facing Fontan Circulatory Failure (FCF). They should be stable enough to participate and not currently awaiting a heart transplant.

Inclusion Criteria

I am an adult with Fontan-associated liver disease affecting my daily activities.

Exclusion Criteria

Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2-fold upper limit of normal (ULN) at screening

Pregnant or planning a pregnancy during the duration of the trial or breastfeeding

Has a baseline systolic blood pressure that is less than 80 mmHg or greater than or equal to 200 mmHg

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either empagliflozin 10 mg once daily or matching placebo for 12 weeks

12 weeks

4 visits (in-person), 3 visits (virtual)

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 study tests if Empagliflozin, a diabetes drug, can improve life quality in FCF patients versus a placebo. Participants are randomly assigned to receive either the medication or an inactive substance.

How Is the Trial Designed?

Group I: Empagliflozin Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Subodh Verma

Lead Sponsor

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Applied Health Research Centre

Collaborator

Trials

23

Recruited

70,900+

Published Research Related to This Trial

In the EMPA-REG OUTCOME trial involving 7020 patients with type 2 diabetes and atherosclerotic cardiovascular disease, empagliflozin significantly reduced the risk of major adverse cardiovascular events, cardiovascular death, and hospitalization for heart failure compared to placebo.

The benefits of empagliflozin were consistent across various levels of baseline cardiovascular risk, indicating its efficacy regardless of prior heart conditions or estimated risk scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Fitchett, D., Inzucchi, SE., Cannon, CP., et al.[2023]

In a study involving 7,020 patients with type 2 diabetes at high cardiovascular risk, empagliflozin significantly reduced the risk of heart failure hospitalization and cardiovascular death compared to placebo, with a hazard ratio of 0.66, indicating a 34% lower risk.

Empagliflozin also improved other heart failure outcomes and reduced all-cause hospitalization rates, demonstrating consistent benefits across patients with and without baseline heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Fitchett, D., Zinman, B., Wanner, C., et al.[2023]

Citations

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

Heart failure outcomes with empagliflozin in patients ... Empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure.

2. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/cv-disease/efficacy

T2D & eCVD Efficacy Data | Jardiance® (empagliflozin) ... In the EMPA-REG OUTCOME trial, JARDIANCE 10 mg and 25 mg reduced the risk of CV death early, and results were consistent for both dosing strengths.

3. acc.org acc.org/Latest-in-Cardiology/Journal-Scans/2024/05/20/17/48/comparative-outcomes-of-empagliflozin

Comparative Outcomes of Empagliflozin to Dapagliflozin in ... Empagliflozin has been shown to result in improved LVEF and functional status compared to dapagliflozin in a single-center retrospective study ...

4. jacc.org jacc.org/doi/10.1016/j.jacc.2024.02.017

Effect of Sodium-Glucose Cotransporter 2 Inhibitors in ... SGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666668524000041

Safety of SGLT-2 inhibitors in the management of heart ... Results. Of the 18 patients, 11 (61%) had moderate complexity congenital heart disease while 7 (39%) had great complexity congenital heart disease. Post ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11811263/

A Systematic Review and Meta-Analysis of the Safety and ... SGLT2is are well tolerated in ACHD HF patients. Notably, SGLT2is improved NYHA FC and reduced NT-proBNP levels across a diverse ACHD HF patient cohort.

7. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2024/04/05/03/00/empact-mi

empact-mi The primary outcome, composite of HF hospitalization or all-cause death, for empagliflozin vs. placebo, was: 5.9 vs. 6.6 events per 100 patient- ...

8. institutionalrepository.aah.org institutionalrepository.aah.org/cgi/viewcontent.cgi?article=1469&context=sciday

Evaluating the Use of Empagliflozin in Pediatric Heart Failure Study Design: • Retrospective observational study. • January 2022-December 2024. Primary Outcome: • Effectiveness of empagliflozin in reducing diuretic.