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

410 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Empagliflozin for treating congenital heart disease?

The research suggests that sodium-glucose co-transporter-2 inhibitors, a class of drugs that includes Empagliflozin, may show benefits in treating heart failure in adults with congenital heart disease. ^{1 2 3 4 5}

Is empagliflozin safe for humans?

Empagliflozin has been shown to reduce the risk of major heart-related events and death in people with type 2 diabetes and heart disease, indicating it is generally safe for humans in these conditions. ^{6 7 8 9 10}

How does the drug Empagliflozin differ from other treatments for congenital heart disease?

Empagliflozin is unique because it is a sodium-glucose co-transporter-2 (SGLT2) inhibitor, which is typically used to manage diabetes by helping the kidneys remove glucose from the bloodstream. Its potential benefit for congenital heart disease lies in its ability to improve heart function, which is different from traditional heart failure treatments that focus on managing symptoms or supporting heart function mechanically. ^{1 11 12 13 14}

What is the purpose of this trial?

Some people are born with a birth defect where they only have one functioning ventricle (lower chamber) in their heart. This condition can be initially managed with a Fontan operation, but there is a risk of developing Fontan Circulatory Failure (FCF) later in life. FCF occurs when the single working heart ventricle is no longer strong enough to pump blood throughout the body. This also means the heart has difficulty supplying oxygen to keep up with the needs of the body. As a result, individuals living with FCF may have some challenges carrying out day to day activities. A heart transplant is currently the only therapeutic option for individuals living with FCF. The investigators are conducting this trial to determine whether a medication called empagliflozin can help these people have a better quality of life.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Heart failure in adults with congenital heart disease. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Identification of risk factors affecting catch-up growth after infant congenital heart disease surgery: rationale and design of a multicentre prospective cohort study in China. [2020]

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

Heart Transplantation and Mechanical Circulatory Support in Adults with Congenital Heart Disease. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A systematic review of the evidence supporting post-operative medication use in congenital heart disease. [2021]

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

Novel Therapeutic Strategies in Heart Failure in Adult Congenital Heart Disease: of Medicines and Devices. [2023]

6. United States 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. [2023]

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

Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin treatment on cardiac function and structure in patients with type 2 diabetes: a cardiac magnetic resonance study. [2020]

9. England 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Cardiovascular Outcomes with Empagliflozin - News for Type 2 Diabetes Therapy. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

Biomarkers of eGFR decline after cardiac surgery in children: findings from the ASSESS-AKI study. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Chronic Kidney Disease in Adolescents after Surgery for Congenital Heart Disease. [2021]

13. Japan pubmed.ncbi.nlm.nih.gov

Continuous-Flow Left Ventricular Assist Device Therapy in Adults with Transposition of the Great Vessels. [2021]

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

Heart failure with reduced and preserved ejection fraction in adult congenital heart disease. [2021]