Empagliflozin for Kidney Transplant Complications

(CREST-KT Trial)

Overseen By Rachael Abuin, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must be taking: Immunosuppressants

Must not be taking: SGLT2i, Anticoagulants

Disqualifiers: Type I diabetes, Other transplants, 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: 8

Duration: 18 months

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called empagliflozin to determine its effectiveness in helping people with kidney transplants, regardless of type 2 diabetes status. The goal is to assess whether empagliflozin can reduce complications after a kidney transplant. Participants will receive either the medication or a placebo (a pill with no active drug) to compare effects. Individuals who had a kidney transplant at least a year ago and are on certain standard medications might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be using SGLT2 inhibitors (a type of diabetes medication) or active anticoagulants (blood thinners) other than low-dose aspirin.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that empagliflozin is generally safe for people with kidney transplants. In studies, it helped control blood sugar in transplant patients without causing major problems and lowered the risk of kidney disease and heart issues compared to a placebo.

Some mild side effects, such as dehydration or urinary tract infections, might occur, but they are usually manageable. Empagliflozin is already approved for other uses, indicating its well-established safety. However, since this trial is in an early stage, researchers are still learning how it specifically affects kidney transplant patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Empagliflozin is unique because it offers a novel approach to managing kidney transplant complications, particularly for patients with or without Type II diabetes. Unlike traditional treatments that primarily focus on immune suppression to prevent rejection, Empagliflozin is a medication that works by inhibiting the sodium-glucose co-transporter 2 (SGLT2). This mechanism not only helps in managing blood sugar levels but also protects kidney function and potentially reduces cardiovascular risks. Researchers are excited about Empagliflozin because it might offer dual benefits—managing diabetes and preserving kidney health—in a way that current standard treatments do not.

What evidence suggests that empagliflozin might be an effective treatment for kidney transplant complications?

Research has shown that empagliflozin, which participants in this trial may receive, could benefit individuals who have had a kidney transplant. Studies have found that it helps control blood sugar levels in those with diabetes post-transplant. Evidence also indicates that it can slow the progression of kidney disease and reduce the risk of heart-related deaths. One study found that empagliflozin reduced the risk of kidney failure by 34%. These benefits occur even if kidney function changes during treatment. Overall, empagliflozin has the potential to improve health outcomes for kidney transplant patients. Participants in this trial will be randomized to receive either empagliflozin or a placebo, regardless of their diabetes status. ^{1 2 3 4 5}

Who Is on the Research Team?

Myles Wolf, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients, with or without type 2 diabetes, who are 12-60 months post-transplant. They must be on standard immunosuppression and have a stable kidney function (eGFR ≥30). Excluded are those with recent severe rejection episodes, pregnant/nursing women, uncircumcised men, active heavy anticoagulant users, Type I diabetics, multiple organ transplants or high hemoglobin A1c levels.

Inclusion Criteria

It has been 1 to 5 years since my kidney transplant.

My kidney function, measured by eGFR, is at least 30ml/min/1.73m^2.

Able to provide written consent

Exclusion Criteria

I have had a solid organ transplant.

I have had more than 2 UTIs in the last year.

I am currently taking SGLT2 inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline

Baseline visit including renal biopsy and 3D echocardiogram

1 week

1 visit (in-person)

Treatment

Participants receive empagliflozin or placebo with follow-up visits every 3 months

18 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• Empagliflozin
• Placebo

Trial Overview

The CREST-KT study tests the effects of Empagliflozin (a diabetes medication) in kidney transplant patients. It's a double-blind trial where participants are randomly assigned to receive either Empagliflozin or a placebo. The ratio of drug to placebo is 2:1 among both diabetic and non-diabetic groups.

How Is the Trial Designed?

Group I: Arm I: With Type II Diabetes Active Control 2 Interventions

Kidney Transplant recipient with Type II diabetes, randomized to either Empagliflozin or a placebo.

Group II: Arm 2: Without Diabetes Active Control 2 Interventions

Kidney Transplant recipient without Type II diabetes, randomized to either Empagliflozin or a placebo

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?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

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 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]

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 (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, 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 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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30862658/

Efficacy and Safety of Empagliflozin in Renal Transplant ...

Conclusions: Empagliflozin appeared safe and improved glycemic control in renal transplant recipients with PTDM compared with placebo. A concomitant reduction ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2204233

Empagliflozin in Patients with Chronic Kidney Disease

Empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo.

3.

thelancet.com

thelancet.com/journals/landia/article/PIIS2213-8587(25)00222-0/fulltext

an individual participant-level meta-analysis

The risk of kidney failure was reduced by 34%. Benefits were evident irrespective of the predicted size of the acute dip in eGFR and ...

4.

nature.com

nature.com/articles/s41467-024-54171-8

The outcomes of SGLT-2 inhibitor utilization in diabetic ...

These findings indicate that SGLT-2i significantly reduces mortality and adverse events in diabetic KTR, underscoring its potential to improve post-transplant ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06013865

Empagliflozin Treatment in Kidney Transplant Recipients

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 ...