Empagliflozin for Congenital Heart Disease

(EmpaCHD Trial)

Recruiting at 2 trial locations

Overseen By Morgan Hindes

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Anita Saraf

Disqualifiers: Diabetes, Liver disease, Metabolic disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of the study is to investigate the feasibility and benefit of novel guideline-directed heart failure therapy drug Empagliflozin (Jardiance) for adult patients with congenital heart disease (ACHD).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently on Jardiance, you must not have taken it in the last 4 weeks to participate.

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

Empagliflozin, a drug originally used for diabetes, has been shown to reduce the risk of death and hospitalization in adults with heart failure, even if they don't have diabetes. It has also been effective in lowering the risk of hospitalization in people with heart failure and improving heart function, which may suggest potential benefits for congenital heart disease. ^{1 2 3 4 5}

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

Empagliflozin is unique because it was originally developed to treat type 2 diabetes by helping the body excrete excess glucose through urine, but it has also been found to reduce the risk of heart failure and cardiovascular death. This makes it different from other treatments for congenital heart disease, which may not have these additional benefits. ^{1 2 6 7 8}

Research Team

Anita Saraf, MD, PhD

Principal Investigator

Assistant Professor

Eligibility Criteria

Adults with congenital heart disease who may be experiencing heart failure can join this trial. Specific details about eligibility are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study or their safety.

Inclusion Criteria

Must be able to complete neurocognitive assessments on a handheld computer.

I am 18 years old or older.

I have been diagnosed with a heart condition present since birth.

Exclusion Criteria

Pregnancy, breastfeeding, or planning to become pregnant in the coming year

I cannot take Jardiance/Entresto or certain heart failure medications due to adverse reactions.

Glomerular Filtration Rate <20

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Empagliflozin 10 mg or placebo daily for 1 year

52 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin

Trial Overview The trial is testing Empagliflozin (Jardiance), a medication for heart failure, against a placebo in adults with congenital heart defects. The aim is to see if it's effective and safe for these patients.

Participant Groups

Group I: Empagliflozin 10 MG Experimental Treatment 1 Intervention

Empagliflozin 10 mg daily will be administered for 1 year. The patient and the PI will be blinded (unaware) of the group they are assigned to.

Group II: Placebo Placebo Group 1 Intervention

Placebo for 1 year

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?

Anita Saraf

Lead Sponsor

Trials

1

Recruited

40+

The Pittsburgh Foundation

Collaborator

Trials

8

Recruited

470+

Findings from Research

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 (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 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]

The EmDia trial is investigating the short-term effects of empagliflozin on left ventricular diastolic function in patients with type 2 diabetes, focusing on the E/E' ratio as a key measure over a 12-week period.

This study aims to provide insights into how empagliflozin may improve cardiovascular outcomes by assessing not only diastolic function but also other cardiovascular measures and molecular biomarkers, enhancing our understanding of its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the effects of EMpagliflozin on left ventricular DIAstolic function in diabetes (EmDia) study. Jünger, C., Prochaska, JH., Gori, T., et al.[2023]

Empagliflozin is effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, which also leads to weight reduction and lower levels of glycated hemoglobin (HbA1C).

Beyond its use in diabetes, empagliflozin has shown significant benefits in heart failure treatment, reducing hospitalizations and cardiovascular deaths, while also providing nephroprotective effects, although it has some limitations and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Insights into the Use of Empagliflozin-A Comprehensive Review. Forycka, J., Hajdys, J., Krzemińska, J., et al.[2023]

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

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]

References

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

Diabetes Drug Now Approved for Heart Failure. [2023]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

Rationale and design of the effects of EMpagliflozin on left ventricular DIAstolic function in diabetes (EmDia) study. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

New Insights into the Use of Empagliflozin-A Comprehensive Review. [2023]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. [2018]

8. Belgium pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]