Empagliflozin for Kidney Failure

Recruiting at 1 trial location

Overseen By Amy J Wigglesworth, RN

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

Trial Summary

What is the purpose of this trial?

The aim of this study is to learn about the safety of empagliflozin in dialysis patients as a preparation for a future large clinical trial. Empagliflozin has been approved by the Food and Drug Administration for the treatment of either type 2 diabetes, heart failure, or chronic kidney disease among patients not on dialysis. The use of empagliflozin has not been studied or approved among patients on dialysis for kidney failure because empagliflozin acts on the kidneys. However, recent experimental studies have indicated that empagliflozin may provide direct heart benefits. Some dialysis patients have substantial residual kidney function, which may be protected by empagliflozin. Participants will be given empagliflozin for three (3) months on top of the standard of care (usual medical care for participants' condition) and will be followed up until one (1) month after the last dose. The investigators will collect information about participants' general health, obtain blood, urine, and imaging studies, check home blood pressure, monitor home blood sugar levels, and ask health-related questions to assess the safety and potential benefits of empagliflozin over four (4) months, including one month before the three (3)-month empagliflozin treatment.

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.

What data supports the effectiveness of the drug empagliflozin for kidney failure?

Empagliflozin has shown benefits in heart failure and type 2 diabetes, including reducing the risk of hospitalization and cardiovascular death, and it has protective effects on the heart and kidneys. While its specific effects on kidney failure are not fully understood, its benefits in related conditions suggest potential effectiveness. ^{1 2 3 4 5}

Is empagliflozin safe for humans?

Empagliflozin, also known as Jardiance, is generally well-tolerated in humans, but it can have side effects like fluid deficits and kidney-related adverse events. It has been studied in people with diabetes, heart failure, and chronic kidney disease, showing some safety concerns that should be monitored by healthcare providers. ^{1 2 3 6 7}

How does the drug empagliflozin differ from other treatments for kidney failure?

Empagliflozin is unique because it not only helps manage blood sugar levels in diabetes but also offers kidney and heart protection, reducing the risk of kidney disease progression and cardiovascular death. It works by blocking a protein in the kidneys that reabsorbs glucose, leading to its excretion in urine, which is different from many other treatments that primarily focus on blood pressure or protein levels. ^{1 2 3 5 8}

Research Team

Yoshitsugu Obi, MD, PhD

Principal Investigator

University of Mississippi Medical Center

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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

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®) 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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Empagliflozin in Patients with Chronic Kidney Disease. [2023]

5. Belgium pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]

6. 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]

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

Empagliflozin Improves Kidney Outcomes in Patients With or Without Heart Failure. [2020]

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

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