Empagliflozin for Kidney Transplant Recipients

(SEKTR Trial)

Recruiting at 4 trial locations

Overseen By Ramesh K Ramalingam

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, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 24 months

264 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Kidney transplantation improves the health and quality of life for those Veterans with end stage kidney disease (ESKD). While early patient and graft survival are excellent, long-term outcomes continue to be challenging. Patient death with existing kidney graft function occurs in about half of all recipients over time. This is primarily due to the development of cardiovascular disease in a patient population with multiple preexisting cardiac disease risk factors. There has been little progress in improving outcomes in this area for over two decades. Recent studies in chronic kidney disease (CKD) patients using SGLT2 inhibitors (SGLT2i), regardless of the presence of type 2 diabetes mellitus (T2DM), results in both kidney protective and cardiac protective impacts and improved patient outcomes. However, kidney transplant recipients (KTRs) were excluded from these clinical trials due to concerns that these agents promote infection, diminish graft function, and may alter immunosuppressive drug levels that are the mainstay of patient's transplant therapy. There are limited published data of SGLT2i treatment of selected KTRs.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used SGLT2 inhibitors in the last 90 days.

Is empagliflozin safe for humans?

Empagliflozin (also known as Jardiance) is generally well-tolerated and used for conditions like heart failure and type 2 diabetes, but it can have side effects such as fluid deficits. It has been studied in people with chronic kidney disease and type 2 diabetes, showing some adverse events, but it is recommended by health guidelines for these conditions. ^{1 2 3 4 5}

How is the drug empagliflozin unique for kidney transplant recipients?

Empagliflozin is unique because it is a sodium glucose cotransporter-2 (SGLT2) inhibitor that not only helps manage blood sugar levels in diabetes but also offers heart and kidney protection, which is beneficial for kidney transplant recipients who often face cardiovascular and kidney-related challenges. ^{1 2 3 6 7}

What data supports the effectiveness of the drug empagliflozin for kidney transplant recipients?

Empagliflozin has been shown to reduce the progression of kidney disease and the risk of cardiovascular problems in patients with chronic kidney disease and type 2 diabetes. It also offers heart and kidney protection, which could be beneficial for kidney transplant recipients. ^{2 3 8 9 10}

Who Is on the Research Team?

Roslyn B Mannon, MD

Principal Investigator

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Are You a Good Fit for This Trial?

This trial is for adult kidney transplant recipients who have type 2 diabetes or post-transplant diabetes, with stable graft function and moderate kidney impairment. They must be able to consent and travel to the VA Medical Center. Exclusions include recent severe infections, uncontrolled diabetes, prior use of SGLT2 inhibitors, certain heart conditions, and a history of significant complications related to diabetes.

Inclusion Criteria

I am over 18 years old.

I have been diagnosed with Type 2 Diabetes or diabetes after an organ transplant.

I can travel to and from the VA Medical Center for my care.

Exclusion Criteria

I have had a pancreas transplant in the past.

I've had more than 2 UTIs this year or was hospitalized for UTI/urosepsis.

I have a fungal infection in my groin or genital area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label Empagliflozin 12.5 mg QD and are monitored for safety and efficacy, including adverse events and impacts on graft function and diabetes management

24 months

Regular visits for monitoring adverse events and treatment efficacy

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on long-term outcomes such as cardiovascular and kidney function

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The study tests Empagliflozin's effects on long-term health outcomes in kidney transplant patients with type 2 diabetes. It aims to see if this medication can protect against heart disease and maintain kidney function without causing harm or interacting negatively with anti-rejection drugs.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

Open Label, Empagliflozin 12.5 mg QD

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+

VA Tennessee Valley Health Care System

Collaborator

Trials

5

Recruited

1,400+

VA Hines Health Care

Collaborator

Nashville VA Medical Center

Collaborator

Trials

4

Recruited

770+

Iowa City VA Health Care System

Collaborator

Trials

4

Recruited

35,700+

VA Pittsburgh Healthcare System

Collaborator

Trials

36

Recruited

15,900+

Published Research Related to This Trial

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]

In the EMPA-KIDNEY trial involving 6609 patients with chronic kidney disease, empagliflozin significantly reduced the risk of kidney disease progression or death from cardiovascular causes compared to placebo, with a hazard ratio of 0.72, indicating a 28% lower risk.

Patients taking empagliflozin also experienced fewer hospitalizations for any cause compared to those on placebo, suggesting a potential safety benefit, although there were no significant differences in heart failure hospitalizations or overall mortality between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin in Patients with Chronic Kidney Disease. Herrington, WG., Staplin, N., Wanner, C., et al.[2023]

In the EMPA-KIDNEY trial involving 6609 participants, empagliflozin significantly slowed the progression of chronic kidney disease, reducing the chronic decline in kidney function by 50% after an initial dip in eGFR.

The benefits of empagliflozin were observed across various patient groups, indicating that albuminuria levels should not be the sole factor in deciding treatment with SGLT2 inhibitors, as even patients with low albuminuria experienced significant improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

The EMPA-KIDNEY study evaluated the effects of empagliflozin in patients with chronic kidney disease, demonstrating significant benefits in slowing the progression of kidney disease.

This study involved a large cohort of patients, providing robust evidence for the efficacy of empagliflozin as a treatment option for chronic kidney disease, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. Kwong, YD., Hsu, CY.[2023]

In a study of 7020 patients with type 2 diabetes and chronic kidney disease, empagliflozin significantly reduced the risk of cardiovascular death by 29% and all-cause mortality by 24% compared to placebo.

Empagliflozin also decreased the risk of hospitalization for heart failure by 39% and all-cause hospitalization by 19%, demonstrating its efficacy in improving clinical outcomes for patients with both diabetes and kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease. Wanner, C., Lachin, JM., Inzucchi, SE., et al.[2022]

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, when administered to 15,081 patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD), showed no new safety concerns, with similar rates of serious adverse events compared to placebo.

The treatment was associated with significantly lower risks of hyperkalemia and edema, suggesting potential benefits for patients with advanced CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Tuttle, KR., Levin, A., Nangaku, M., et al.[2022]

In a study of 213 patients with type 2 diabetes and chronic kidney disease, urinary tract infections and genital mycotic infections were the most common adverse events associated with SGLT2 inhibitors, occurring at rates of 62.1 and 58.0 events per 1000 person-years, respectively.

Despite these adverse events, SGLT2 inhibitors led to favorable changes in kidney function markers, with significant decreases in urine albumin-to-creatinine ratios and hemoglobin A1c percentages, indicating their efficacy in managing diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease: A Retrospective Chart Review. Choi, H., Nguyen, LA., Wan, J., et al.[2022]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. Chen, G., Zhang, D., Du, A., et al.[2021]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

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

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

Empagliflozin in Patients with Chronic Kidney Disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

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

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. [2023]

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

Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease. [2022]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

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

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. [2022]

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

Adverse Events of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease: A Retrospective Chart Review. [2022]

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

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. [2021]

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

SGLT2 inhibitors: new reports. [2019]