Empagliflozin for Heart Transplant Recipients

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

200 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug empagliflozin for heart transplant recipients?

Empagliflozin has been shown to lower the risk of hospitalization in people with heart failure and reduce the risk of cardiovascular death, even in those without diabetes. It is also effective in reducing major cardiovascular events in patients with type 2 diabetes. ^{1 2 3 4 5}

How does the drug empagliflozin differ from other treatments for heart transplant recipients?

Empagliflozin is unique because it is primarily a diabetes medication that also helps reduce the risk of heart-related issues and hospitalizations in heart failure patients, even those without diabetes. It works by preventing glucose reabsorption in the kidneys, which is different from other heart failure treatments. ^{1 2 3 6 7}

What is the purpose of this trial?

Heart transplant (HTx) is an established therapy for advanced heart disease that restores quality of life and improves survival. However, due to preexisting comorbidities combined with the immunosuppressive therapies required after transplantation, HTx recipients remain at high risk for kidney, cardiovascular (CV), and metabolic disease. Large randomized clinical trials have recently shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) have potent kidney protective and CV benefits in many populations of patients with chronic kidney disease (CKD), CV disease and/or diabetes. SGLT2i have not been studied prospectively in HTx recipients, which represents a barrier to their use in this population. In this multicenter randomized controlled trial in Veterans with HTx, investigators will evaluate the potential benefits of empagliflozin on kidney function, cardiometabolic risk, erythropoiesis, and functional status. A total of 200 Veterans will be randomly assigned to receive either empagliflozin 10 mg daily or a matching placebo for 12 months.

Research Team

Josef Stehlik, MD MPH

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 (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]

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 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]

References

1. 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]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

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

Efficacy and Safety of Empagliflozin in the Management of Diabetes Mellitus in Heart Transplant Recipients. [2022]

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

SGLT2 inhibitors: new reports. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. [2022]