Empagliflozin for Dialysis Patients with Kidney Failure

Overseen By Jonathan Gutierrez

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Utah

Disqualifiers: Type 1 diabetes, Malignancy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether empagliflozin, a medication typically used for diabetes, is safe for people on dialysis. While it is known to help prevent heart problems in others, it has not yet been tested on dialysis patients. Participants will take either a low dose, a higher dose, or a placebo (a pill with no active medication) for 12 weeks. Those on dialysis for at least three months, who do not have type 1 diabetes or certain other conditions, might be suitable candidates. The goal is to determine if this drug could eventually help reduce heart issues in dialysis patients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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

The protocol does not specify if you need to stop taking your current medications. However, it does not mention any specific requirements to stop or continue existing medications.

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

Research has shown that empagliflozin is generally safe for people with chronic kidney disease (CKD). Studies have not identified new safety issues for those with type 2 diabetes and advanced CKD, meaning patients did not experience unexpected side effects. However, the risk of urinary tract infections is higher, especially in women.

Empagliflozin has approval for other conditions, indicating it is well-tolerated by many patients. It is important to note that this trial is in an early stage, so researchers are still studying the safety of empagliflozin in dialysis patients. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney failure?

Researchers are excited about empagliflozin for kidney failure patients undergoing dialysis because it offers a new approach to managing their condition. Unlike standard treatments that focus on controlling blood pressure or managing electrolyte balance, empagliflozin works by inhibiting the sodium-glucose co-transporter 2 (SGLT2), which can provide cardiovascular and renal protective benefits. This mechanism not only helps control blood sugar levels but also has the potential to improve heart and kidney outcomes, which is especially promising for dialysis patients who often face severe cardiovascular risks.

What evidence suggests that this trial's treatments could be effective for dialysis patients with kidney failure?

Research has shown that empagliflozin can lower the risk of worsening kidney disease and heart-related deaths in people with chronic kidney disease. Studies have found that it slows kidney damage and reduces the chances of heart failure and hospital visits for heart issues. Specifically, empagliflozin can lower the risk of kidney failure by 34%. It also benefits both diabetic and non-diabetic patients with heart problems. Although earlier studies did not include patients on dialysis, this trial will evaluate its potential benefits for dialysis patients. Participants in this trial will receive either empagliflozin at 10mg or 25mg, or a placebo, to assess its effectiveness in this specific population. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with severe chronic kidney disease (ESKD) who have been on dialysis for at least 3 months, regardless of whether they have diabetes. It's not open to those with active cancer treatment, unhealed skin ulcers on the lower body, allergies to empagliflozin, pregnancy, type 1 diabetes, current IV antibiotic therapy for infections, a history of Fournier's gangrene or recent severe hypoglycemia.

Inclusion Criteria

I have been on dialysis for 3 months or more.

I am an adult, with or without diabetes.

Exclusion Criteria

You have had very low blood sugar that needed help from someone else in the past year.

I am currently receiving treatment for cancer.

You are allergic to empagliflozin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive 10 mg QD for the first 2 weeks before escalating the dose to 25 mg QD in week 3, based on tolerability

4 weeks

Weekly visits (in-person)

Treatment

Participants continue the randomized assignment for additional 8 weeks, receiving either 10 mg or 25 mg QD, or placebo

8 weeks

Bi-weekly 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

• Empagliflozin
• Placebo

Trial Overview The study tests if empagliflozin is safe and can be tolerated by patients dependent on dialysis due to ESKD. Empagliflozin has helped prevent heart failure in diabetic and non-diabetic patients but hasn't been studied in those with advanced kidney disease undergoing dialysis.

How Is the Trial Designed?

Group I: Empagliflozin 25mg Experimental Treatment 1 Intervention

Empagliflozin 25 mg oral: Those randomized to 25 mg daily dose will be treated with 10 mg QD for the first 2 weeks before escalating the dose to 25 mg QD in week 3, based on tolerability. At the end of the dose-escalation phase (weeks 3-4), participants will continue the randomized assignment for additional 8 weeks (weeks 5-12, treatment phase), for a total of 12 weeks.

Group II: Empagliflozin 10mg Experimental Treatment 1 Intervention

Empagliflozin10mg oral: Those randomized to 10 mg daily dose will be treated with 10 mg QD throughout the dose escalation and the treatment phase for a total of 12 weeks.

Group III: Placebo Placebo Group 1 Intervention

Encapsulated placebo with an identical appearance to empagliflozin: Those randomized to placebo will be treated with an oral placebo QD throughout the dose escalation and the treatment phase for a total of 12 weeks.

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 Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

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]

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]

The EMPA-KIDNEY trial is a large-scale study involving 6609 participants with chronic kidney disease (CKD) to assess the efficacy and safety of empagliflozin in reducing the risk of kidney disease progression and cardiovascular death.

Participants included individuals with varying degrees of kidney function and both diabetic and non-diabetic patients, making the results applicable to a broad population at risk for CKD complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of 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]

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 (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 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]

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. 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.

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. jacc.org jacc.org/doi/10.1016/j.jacc.2023.03.390

Efficacy of Empagliflozin in Patients With Heart Failure ... Empagliflozin reduced the risk for cardiovascular death or hospitalizations for heart failure and slowed the rate of decline in eGFR in all ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39836391/

Effectiveness of Empagliflozin vs Dapagliflozin for Kidney ... Main outcomes and measures: Outcomes included acute kidney injury, incident chronic kidney disease (stages G3 to G5 or stage A2 or A3), and ...

6. 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 ...

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

Safety of Empagliflozin: An Individual Participant-Level ... The risk of urinary tract infections, including those that spread to the kidneys, was higher for women taking empagliflozin versus placebo.

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

Safety Profile for CKD | Jardiance® (empagliflozin) tablets The primary endpoint was a composite of: sustained decrease in eGFR of ≥40% from baseline, sustained decrease in eGFR to <10 mL/min/1.73 m2, ESKD (the ...