Empagliflozin for Heart Transplant Recipients

Not yet recruiting at 5 trial locations

Overseen By Josef Stehlik, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Multiorgan transplant, 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: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if empagliflozin, a medication known to support kidney and heart health, can benefit individuals who have undergone a heart transplant. Researchers will assess whether this drug can enhance kidney function, heart health, and overall physical condition. Participants will receive either empagliflozin or a placebo (a harmless pill with no active medicine) for one year. The study seeks heart transplant recipients who are at least three months post-surgery. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit additional 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 taking SGLT2 inhibitors, you must stop at least 30 days before joining the trial.

What is the safety track record for empagliflozin?

Research has shown that empagliflozin is generally easy for patients to handle. One study linked only three possible side effects to the treatment. Another study involving over 75,000 patients found that empagliflozin is safe for most people. However, researchers have not specifically tested it in heart transplant recipients before now. While some risk of side effects always exists, the evidence so far appears promising for empagliflozin's safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Empagliflozin is unique because it targets heart transplant recipients in a new way. While most treatments for heart transplant recipients focus on immune suppression to prevent rejection, empagliflozin is primarily known for its role in managing blood sugar levels in diabetes. Researchers are excited about empagliflozin because it offers a potential dual benefit of protecting the heart by improving metabolic health and possibly reducing heart failure risks. This innovative approach could improve overall outcomes for heart transplant patients beyond the standard immune-suppressing therapies.

What evidence suggests that empagliflozin might be an effective treatment for heart transplant recipients?

Research has shown that empagliflozin can improve heart health and control blood sugar in people with diabetes, including those who have had heart transplants. For example, one study found it lowered the risk of death from heart problems and reduced hospital visits for heart failure. Another study demonstrated that it safely improved blood sugar levels in heart transplant patients with diabetes. Empagliflozin also protects the kidneys and benefits people with heart disease. In this trial, participants will receive either empagliflozin or a placebo to evaluate its potential benefits in helping heart transplant patients better manage their heart and kidney health. ^{1 2 3 4 6}

Who Is on the Research Team?

Josef Stehlik, MD MPH

Principal Investigator

VA Salt Lake City Health Care System, Salt Lake City, UT

Are You a Good Fit for This Trial?

This trial is for heart transplant recipients who may have kidney, cardiovascular, or metabolic issues due to their condition and post-transplant medications. It's specifically designed for Veterans who've undergone a heart transplant.

Inclusion Criteria

I received a heart transplant more than 3 months ago.

Exclusion Criteria

Known allergy or intolerance to SGLT2i

HbA1C >10%

My urine protein levels are low and I don't have type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Testing

Baseline testing is conducted before randomization and initiation of treatment

1-2 weeks

Treatment

Participants receive either empagliflozin 10 mg daily or a matching placebo for 12 months

12 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 study tests whether empagliflozin can improve kidney function, reduce the risk of heart and metabolic diseases, boost red blood cell production, and enhance overall physical health in these patients compared to a placebo.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

A starting dose of empagliflozin 10 mg or matching placebo will be initiated after randomization and completion of the baseline testing. Participating subjects will remain at this dose for the whole study duration of 12 months.

Group II: Placebo Placebo Group 1 Intervention

A starting dose of empagliflozin 10 mg or matching placebo will be initiated after randomization and completion of the baseline testing. Participating subjects will remain at this dose for the whole study duration of 12 months.

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

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 (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]

Empagliflozin (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

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 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/PMC12255340/

Empagliflozin Use in Cardiac Transplant Patients

Moreover, patients who used empagliflozin experienced a decreased risk of cardiovascular mortality. This landmark trial shifted clinicians' focus from a ...

2.

journals.lww.com

journals.lww.com/transplantationdirect/fulltext/2019/05000/efficacy_and_safety_of_empagliflozin_in_the.9.aspx

Efficacy and Safety of Empagliflozin in the Management of...

These data suggest empagliflozin was efficacious for improving glycemic control in heart transplant patients with diabetes mellitus relative to treatment using ...

3.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1504720

Empagliflozin, Cardiovascular Outcomes, and Mortality in ...

The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the ...

4.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/joim.20077

Effects of SGLT2 inhibitors on transplant survival and key ...

Both studies showed that empagliflozin is safe and effective in the treatment of diabetes in patients with cardiac transplants. In another study ...

5.

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: ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06625073

Randomized Trial of SGLT2i in Heart Transplant Recipients

SGLT2i have been tested prospectively in >75,000 patients and demonstrated a favorable safety profile. Exclusion of organ transplant recipients from these ...