Empagliflozin for Kidney Failure

Recruiting at 1 trial location

Overseen By Rachael Thompson

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Mississippi Medical Center

Must not be taking: SGLT2 inhibitors

Disqualifiers: Low blood pressure, Cancer, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety of empagliflozin in patients with kidney failure who are on dialysis. Although empagliflozin is approved for conditions like type 2 diabetes and heart failure, its effects on dialysis patients remain unclear. The study will involve patients taking different doses of empagliflozin to determine if it can offer heart benefits and protect any remaining kidney function. Ideal participants have end-stage kidney disease and are currently undergoing dialysis. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you will continue with your usual medical care while taking empagliflozin.

Is there any evidence suggesting that empagliflozin is likely to be safe for dialysis patients?

Research shows that empagliflozin is generally safe for people with chronic kidney disease (CKD). One study found that those taking empagliflozin had a lower risk of worsening kidney disease or dying from heart problems compared to those not taking the drug. It also showed a reduced risk of kidney injury for those on empagliflozin.

The FDA has approved empagliflozin for treating type 2 diabetes, heart failure, and CKD in patients not on dialysis, indicating it has been tested for safety in these groups. However, it has not been studied in people on dialysis until now.

In other studies, some people taking empagliflozin experienced side effects like genital infections and low blood sugar, but these were uncommon. Overall, past research indicates that empagliflozin is safe for people with kidney problems, but its effects on dialysis patients are still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about empagliflozin for kidney failure because it offers a novel approach compared to the current treatment options like ACE inhibitors or ARBs. Most existing treatments focus on controlling blood pressure and reducing protein in the urine to slow kidney damage. However, empagliflozin works differently by targeting glucose reabsorption in the kidneys, which may help protect kidney function in a new way. Additionally, one treatment approach involves a 10 mg daily dosage that can be administered to patients on various dialysis schedules, while another involves a 25 mg dosage taken after dialysis sessions, offering tailored options for different patient needs. These innovative features have the potential to enhance treatment effectiveness and improve quality of life for patients with kidney failure.

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

Research has shown that empagliflozin can slow chronic kidney disease and reduce the risk of kidney failure by 34%. This treatment also benefits heart health by lowering the risk of death from heart-related issues. Earlier studies demonstrated improvements in kidney function, with better filtration rates and lower creatinine levels, which indicate kidney health. In this trial, participants will receive either empagliflozin 10 mg daily or empagliflozin 25 mg thrice-weekly post-hemodialysis. Although researchers have not studied empagliflozin in patients on dialysis, some of these patients may still have enough kidney function to benefit from the drug. These findings suggest that empagliflozin could effectively protect and improve kidney and heart health. ^{1 6 7 8 9}

Who Is on the Research Team?

Yoshitsugu Obi, MD, PhD

Principal Investigator

University of Mississippi Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with end-stage kidney disease on dialysis. They must be able to consent and not have had recent major surgery, active cancer, heart or liver transplants, severe low blood pressure before dialysis, certain infections or urinary issues in the past year, advanced heart failure needing devices or drugs to help the heart work, liver cirrhosis, a history of ketoacidosis within a year, known allergies to SGLT2 inhibitors like empagliflozin.

Inclusion Criteria

I am on dialysis for end-stage kidney disease.

I am on dialysis for end-stage kidney disease.

Ability to provide informed consent

Exclusion Criteria

I am allergic to SGLT2 inhibitors.

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

I currently have active cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Run-in

Participants undergo a run-in period before starting the treatment

4 weeks

Treatment

Participants receive empagliflozin for 3 months on top of the standard of care

12 weeks

Regular visits for monitoring and data collection

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 if empagliflozin is safe for patients on dialysis due to kidney failure. It explores two dosing methods: one takes 25 mg after each hemodialysis session (thrice-weekly), and another takes 10 mg daily. Participants will also receive standard medical care during the three-month treatment period plus follow-up for an additional month.

How Is the Trial Designed?

Group I: Empagliflozin 25 mg thrice-weekly post-hemodialysis dosing Experimental Treatment 1 Intervention

All participants undergoing thrice-weekly hemodialysis (HD) on the Monday-Wednesday-Friday (MWF) schedule will be assigned to the empagliflozin 25 mg thrice-weekly post-hemodialysis dosing arm (Group I).

Group II: Empagliflozin 10 mg daily dosing Experimental Treatment 1 Intervention

Patients undergoing thrice-weekly hemodialysis (HD) on the Tuesday-Thursday-Saturday (TTS) schedule, patients on twice-weekly HD, or patients on peritoneal dialysis will receive empagliflozin 10 mg daily (Group II).

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?

University of Mississippi Medical Center

Lead Sponsor

Trials

185

Recruited

200,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

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]

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 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]

In the EMPA-REG OUTCOME trial, empagliflozin significantly reduced the risk of worsening kidney outcomes and cardiovascular death by 43% in patients with heart failure, demonstrating its efficacy in managing kidney health in type 2 diabetes patients.

Empagliflozin stabilized estimated glomerular filtration rate over time, contrasting with a gradual decline seen in the placebo group, indicating its potential to slow chronic kidney disease progression regardless of heart failure status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin Improves Kidney Outcomes in Patients With or Without Heart Failure. Butler, J., Zannad, F., Fitchett, D., et al.[2020]

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, 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]

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]

Citations

1. 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.

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7615591/

Effects of Empagliflozin on Progression of Chronic Kidney ... Empagliflozin slowed the rate of progression of CKD among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182543/

Impact of Empagliflozin on Cardiovascular Outcomes and ... Renal function improved significantly, with a rise in estimated glomerular filtration rate (eGFR) and a decline in serum creatinine levels (p < ...

5. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/payor/vital-perspectives/jardiance/clinical/guidelines/ckd

Guidelines - Chronic Kidney Disease | Jardiance Clinical Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including JARDIANCE.

6. patient.boehringer-ingelheim.com patient.boehringer-ingelheim.com/us/products/jardiance/chronic-kidney-disease

Chronic Kidney Disease | Jardiance® (empagliflozin) tablets JARDIANCE is used to reduce risk of further worsening of kidney disease, ESKD, CV death, and hospitalization in adults with CKD. See Safety/PI Med Guide.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213770/

Safety of Empagliflozin: An Individual Participant-Level ... The risk of kidney injury was reduced in patients taking empagliflozin versus placebo. The risk of genital infections, hypoglycemia, bone ...

8. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/ckd/safety

Safety Profile for CKD | Jardiance® (empagliflozin) tablets See the JARDIANCE safety profile in the EMPA-KIDNEY trial for adult patients with chronic kidney disease. View Safety, PI and Med Guide.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9210861/

Safety of Empagliflozin in Patients With Type 2 Diabetes ... Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of ...