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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Empagliflozin, a heart failure medication, can assist adults with congenital heart disease (heart defects present from birth). Researchers seek to discover if this drug can enhance heart function and quality of life. Participants will receive either the actual medication or a placebo (a harmless pill that looks the same) without knowing which one they receive. This trial suits adults with a specific form of congenital heart disease who have experienced a decline in heart efficiency over the past six months. As a Phase 4 trial, Empagliflozin is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

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 is the safety track record for Empagliflozin?

Research has shown that empagliflozin is generally safe and well-tolerated in people with heart conditions, including congenital heart defects. Studies have found that this drug can improve heart function and reduce certain heart-related risks. Specifically, empagliflozin has been linked to fewer hospital visits and deaths from heart issues compared to other treatments.

A detailed review found that empagliflozin did not cause major changes in blood pressure or kidney function, which are important for safety. Overall, users of empagliflozin reported fewer serious side effects, making it a promising option for heart patients.

Empagliflozin is also approved by the FDA for other uses, supporting its safety profile. However, as with any medication, discussing potential risks and benefits with healthcare providers is important before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for congenital heart disease, which often involve surgical interventions or medications like beta-blockers and ACE inhibitors, empagliflozin offers a novel approach by working as an SGLT2 inhibitor. This class of drugs is traditionally used for managing blood sugar in diabetes but has shown promise in improving heart function. Researchers are excited about empagliflozin because it targets glucose regulation and may help reduce heart strain, potentially offering a less invasive treatment option with unique benefits for heart health.

What is the effectiveness track record for Empagliflozin in treating congenital heart disease?

Research has shown that Empagliflozin, also known as Jardiance, works well for heart failure. In people with congenital heart disease (ACHD), studies have found that it improves heart function and lowers certain heart-related markers. Empagliflozin also reduces the risk of hospitalization for heart issues. Patients generally tolerate it well. This trial will compare Empagliflozin 10 mg daily with a placebo to evaluate its effectiveness and safety in this specific population. The treatment has been approved for heart failure in other situations, demonstrating its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Anita Saraf, MD, PhD

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

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 have been diagnosed with a heart condition present since birth.

My heart condition is moderately to highly complex.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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 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 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]

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]

Citations

1.

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.

2.

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, ...

3.

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 ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11490347/

Empagliflozin Use Is Associated With Lower Risk of All-Cause ...

Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients ...

5.

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 ...

6.

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.