Empagliflozin for Kidney Failure

(SEED Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by David Charytan, MS, MSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NYU Langone Health

Must not be taking: SGLT2 inhibitors, ACEi and ARB

Disqualifiers: Anuria, Heart failure, Liver disease, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing empagliflozin, a medication that lowers blood sugar, in patients with severe kidney disease who are beginning treatment. The goal is to see if it is safe and effective for these patients. Empagliflozin helps the body get rid of extra sugar through urine.

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 use an SGLT2 inhibitor within 6 weeks before joining the study. Also, you cannot use both an ACE inhibitor and an angiotensin receptor blocker together.

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

Research shows that empagliflozin can reduce the risk of kidney disease progression and cardiovascular death in patients with chronic kidney disease and type 2 diabetes. It also helps stabilize kidney function over time, even in patients with heart failure. ^{1 2 3 4 5}

Is empagliflozin safe for humans?

Empagliflozin, also known as Jardiance, has been studied for safety in people with type 2 diabetes and chronic kidney disease. Clinical trials have shown that it is generally safe, but patients should be monitored for potential side effects like fluid deficits. ^{1 2 4 5 6}

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 slows the progression of kidney disease and reduces the risk of cardiovascular death, making it beneficial for patients with chronic kidney disease and heart failure. ^{1 2 4 7 8}

Eligibility Criteria

Adults over 18 who recently started hemodialysis for end-stage kidney disease can join this trial. They must be able to consent and, if female and able to have children, show a negative pregnancy test. People with plans for a kidney transplant soon, severe heart failure, recent major cardiovascular events or surgery, certain diabetes types or complications, active serious infections or cancer treatments are excluded.

Inclusion Criteria

I am 18 or older and started hemodialysis within the last 6 months.

I am on a thrice-weekly hemodialysis schedule.

I am of childbearing age and have a negative pregnancy test.

Exclusion Criteria

I am currently receiving treatment for cancer, except for certain skin cancers and early-stage cervical cancer.

I have had more than 2 urinary tract infections in a year.

I am unable to understand and give consent for medical procedures.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Empagliflozin or placebo daily for 12 weeks while initiating hemodialysis

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin 10 MG (Sodium-glucose cotransporter 2 (SGLT2) inhibitor)
• Placebo (Drug)

Trial Overview The study is testing the safety and potential benefits of Empagliflozin (a diabetes medication) in patients on hemodialysis due to chronic kidney failure. Participants will either receive Empagliflozin or a placebo without knowing which one they're getting for 12 weeks to compare outcomes.

Participant Groups

Group I: Empagliflozin Experimental Treatment 1 Intervention

Participants with end-stage kidney disease (ESRD) initiating hemodialysis will receive Empagliflozin 10 mg daily for 12 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants with ESRD initiating hemodialysis will receive Empagliflozin-matching placebo daily for 12 weeks.

Empagliflozin 10 MG is already approved in United States, European Union, Australia for the following indications:

🇺🇸 Approved in United States as Jardiance for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

🇪🇺 Approved in European Union as Jardiance for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

🇦🇺 Approved in Australia as Jardiance for:

• Type 2 diabetes
• Chronic kidney disease

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Brigham and Women's Hospital Boston, MA

NYU Langone Health New York, NY

Who Is Running the Clinical Trial?

NYU Langone Health Lead Sponsor

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

Boehringer Ingelheim Industry Sponsor

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] Label="SOURCE CITATION">EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388:117-27. 36331190.

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

Empagliflozin Improves Kidney Outcomes in Patients With or Without Heart Failure. [2020] Background In EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) empagliflozin significantly reduced the risk of cardiovascular and kidney outcomes in patients with type 2 diabetes mellitus and established cardiovascular disease. Post hoc, we evaluated empagliflozin on kidney outcomes in patients with or without heart failure (HF). Methods and Results Individuals were randomized to empagliflozin 10 mg, 25 mg, or placebo. Prespecified analyses by baseline HF status included risk of incident or worsening nephropathy and estimated glomerular filtration rate slope analyses. Cox proportional hazards models assessed consistency of treatment effect across subgroups. Safety evaluations included kidney-related adverse events. At baseline, 244 (10.5%) and 462 (9.9%) patients had HF in the placebo and empagliflozin groups, respectively. Overall, the incidence of kidney outcome events was numerically higher in patients with than without HF. In the HF group, empagliflozin reduced risk of incident or worsening nephropathy or cardiovascular death by 43% (hazard ratio, 0.57 [95% CI, 0.42-0.77]) and progression to macroalbuminuria by 50% (hazard ratio, 0.50 [0.33-0.75]). After an initial transient decrease, estimated glomerular filtration rate stabilized over time with empagliflozin but gradually declined with placebo. Kidney effects in patients with HF were consistent with those in the overall study population (all P values for interaction >0.05). Across groups, the incidence rate of kidney-related adverse events/100 patient-years was higher in patients with than without HF; however, overall rates were comparable between groups. Conclusions These findings from EMPA-REG OUTCOME support the hypothesis that empagliflozin could reduce the risk of clinically relevant kidney events and may slow progression of chronic kidney disease in individuals with type 2 diabetes mellitus regardless of HF status. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01131676.

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

Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial. [2023] In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin.

4. 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] To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials.

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

Diabetes Drug Now Approved for Heart Failure. [2023] The diabetes drug empagliflozin (Jardiance) is now approved to reduce the risk of cardiovascular death and hospitalization in adults with heart failure, even if they do not have diabetes.Nurses and NPs should monitor patients for adverse effects, especially fluid deficits.

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

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. [2021] To evaluate the pharmacokinetic properties and safety of empagliflozin, and the bioequivalence of test formulation empagliflozin tablet compared with the brand-name drug Jardiance (reference formulation) after single oral administration under fasting and fed conditions in healthy Chinese subjects.

7. Germany pubmed.ncbi.nlm.nih.gov

[Chronic Kidney Disease - Update 2018]. [2019] SGLT2-INHIBITION IN DIABETIC AND NON-DIABETIC KIDNEY DISEASE: The CANVAS Program Collaborative Group study confirmed nephroprotective actions by canagliflocin comparable to empagliflozin as published in the EMPA-REG Outcome study. Treatment with Liraglutide (LEADER study) also suggests nephroprotection via albuminuria reduction a decreased eGFR decline in subgroups and depending on stages of diabetic nephropathy. KDIGO CKD-MBD GUIDELINE UPDATE 2017: In July 2017, an update of the KDIGO (Kidney Disease: Improving Global Outcomes) 2009 guideline on diagnostic and treatment chronic kidney disease - mineral and bone disorders (CKD-MBD) was published. Changes focused on the judgement of bone mineral density measurements, therapy of hyperphosphatemia and secondary hyperparathyroidism in CKD patients not on dialysis and on advising caution concerning excess calcium exposition.

8. Switzerland pubmed.ncbi.nlm.nih.gov

Renal and Glucose-Lowering Effects of Empagliflozin and Dapagliflozin in Different Chronic Kidney Disease Stages. [2019] Objective: The objective of this study was to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal function in different stages of chronic kidney disease (CKD). Design and Methods: We conducted a retrospective cohort study using longitudinal claims data from May 2016-December 2017 from the Chang Gung Research Database. Patients who used one of the three types of SGLT2 inhibitor available at Chang Gung Memorial Hospital, namely empagliflozin 10 mg/tab (Empa10), empagliflozin 25 mg/tab (Empa25), and dapagliflozin 10 mg/tab (Dapa), were included, with the same number of matched non-users. Analysis of variance was used for continuous variables and the chi-square test was applied for categorical variables. Differences in data between two groups were analyzed using an independent t-test, and the basic data before and after treatment were analyzed using generalized estimating equation (GEE). The association among renal function changes was analyzed using a Cox proportional hazards model, with the results presented as unadjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: Among the 7,624 SGLT2 inhibitor users, 1,696 patients used Empa10, 2,654 used Empa25, and 3,274 used Dapa. Compared with non-users, dapagliflozin had the lowest risk of estimated glomerular filtration rate (eGFR) decrease over 40% from baseline within 1 year (HR 0.36, 95% CI 0.25-0.51). By using the ICD-10-CM code N179, the acute kidney injury (AKI)-related hospitalization rate was lower in Empa10 and Dapa users than in non-users (HR 0.65, 95% CI 0.49-0.86). Conclusion: Lower risk of eGFR decrease over 40% and AKI-related hospitalization was found in all SGLT2 inhibitor users across the different CKD stages.