Empagliflozin for Dialysis Patients with Kidney Failure

Overseen By Jonathan Gutierrez

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Utah

Disqualifiers: Type 1 diabetes, Malignancy, Pregnancy, others

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if empagliflozin, a new diabetic medication that has been shown to be very effective in lowering the risk of heart failure, is safe and tolerated in dialysis patients. In the recent years, empagliflozin has become a major tool to prevent heart failure hospitalization and to reduce the risk for cardiovascular death in diabetic and non-diabetic patients. Although patients with severe chronic kidney disease and ESKD have very high risk of heart failure and cardiovascular death, they have been excluded from all of the previous studies. If this medication is found to be well tolerated and safe in dialysis patients through this study, future clinical studies can evaluate if this medication can also reduce the risk of heart failure and cardiovascular death in dialysis patients.

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.

What data supports the idea that Empagliflozin for Dialysis Patients with Kidney Failure is an effective drug?

The available research shows that empagliflozin, while primarily studied for heart failure and diabetes, has shown benefits in patients with chronic kidney disease (CKD). Specifically, the EMPA-KIDNEY trial found that empagliflozin reduced the progression of kidney disease or the risk of cardiovascular death over two years. This suggests that empagliflozin could be effective for patients with kidney failure, even though the direct evidence for dialysis patients is not detailed in the provided information. ^{1 2 3 4 5}

What safety data exists for empagliflozin in dialysis patients with kidney failure?

Empagliflozin, also known as Jardiance, has been studied for safety in patients with type 2 diabetes and chronic kidney disease (CKD) in placebo-controlled clinical trials. It is approved for reducing cardiovascular death and hospitalization in heart failure patients, even without diabetes. While generally well-tolerated, it has side effects and contraindications, particularly fluid deficits, which should be monitored. The EMPA-KIDNEY trial is investigating its effects on renal and cardiovascular disease in CKD patients. ^{1 2 3 6 7}

Is the drug Empagliflozin a promising treatment for dialysis patients with kidney failure?

Yes, Empagliflozin is a promising drug for dialysis patients with kidney failure. It helps protect the heart and kidneys, reduces the risk of heart failure, and slows down kidney disease progression. It is also effective in managing diabetes and can lower blood pressure and body weight. ^{1 2 3 4 8}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Empagliflozin (Sodium-glucose cotransporter 2 (SGLT2) inhibitor)
• Placebo (Other)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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 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-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, 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]

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]

References

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

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

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

Empagliflozin in Patients with Chronic Kidney Disease. [2023]

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. England pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. [2023]

8. Belgium pubmed.ncbi.nlm.nih.gov

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