Empagliflozin for Kidney Failure

(SEED Trial)

Recruiting at 1 trial location

Overseen By Finnian R. Mc Causland

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: SGLT2 inhibitors, ACEi and ARB

Disqualifiers: Anuria, Heart failure, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests empagliflozin, a medication, to determine its safety and effectiveness for people with end-stage kidney disease who are starting hemodialysis. The researchers aim to compare the effects of empagliflozin with a placebo (a non-active substance) over a 12-week period. Suitable candidates for this trial include those on regular hemodialysis who retain some kidney function and can provide informed consent. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

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

Research shows that empagliflozin is usually well-tolerated by patients. Studies have found that it can lower the risk of worsening kidney disease and reduce deaths from heart-related issues compared to a placebo. For people with chronic kidney disease, empagliflozin has been shown to slow the disease's progression.

However, some risks exist. In certain cases, empagliflozin and similar drugs have caused sudden kidney problems, which may require hospitalization and dialysis. This has been observed in patients with type 2 diabetes using drugs like empagliflozin.

Since this trial is in phase II, empagliflozin has already undergone safety testing in earlier trials. This phase focuses more on how well the treatment is tolerated and its effectiveness. Joining the trial could help researchers learn more about the safety and benefits of empagliflozin for people starting hemodialysis. ^{1 2 3 4 5}

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

Unlike the standard treatments for end-stage kidney disease, which often focus on managing symptoms and slowing progression, Empagliflozin offers a unique approach by targeting glucose reabsorption in the kidneys. This mechanism not only helps control blood sugar levels but also has potential kidney-protective effects, which could be particularly beneficial for patients initiating hemodialysis. Researchers are excited about Empagliflozin because it could address multiple aspects of the disease, potentially improving both cardiovascular and renal outcomes for patients with kidney failure.

What evidence suggests that empagliflozin might be an effective treatment for end-stage kidney disease?

Research shows that empagliflozin can help slow chronic kidney disease (CKD). In earlier studies, participants who took empagliflozin had a lower risk of worsening kidney disease or dying from heart problems compared to those who took a placebo. Empagliflozin also slightly improved quality of life and reduced hospital visits. In this trial, participants with end-stage kidney disease (ESRD) starting hemodialysis will receive either empagliflozin or a placebo to assess its effectiveness for this advanced stage of kidney disease. ^{1 2 3 4 6}

Who Is on the Research Team?

David Charytan, MS, MSc

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin 10 MG
• Placebo

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.

How Is the Trial Designed?

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 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

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

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]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

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. Chen, G., Zhang, D., Du, A., et al.[2021]

In the EMPA-REG Outcome trial involving 6952 patients with type 2 diabetes and established cardiovascular disease, empagliflozin significantly reduced the risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and worsening kidney disease by 39% compared to placebo.

The efficacy of empagliflozin was consistent across different Kidney Disease Improving Global Outcomes (KDIGO) risk categories, indicating that its benefits on cardiovascular and kidney outcomes were not influenced by the patients' baseline chronic kidney disease status, although it was associated with a higher rate of genital infections.

NCBI (Pubmed)

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. Levin, A., Perkovic, V., Wheeler, DC., 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 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 CANVAS Program study confirmed that canagliflozin has nephroprotective effects similar to empagliflozin, indicating that SGLT2 inhibitors can be beneficial for both diabetic and non-diabetic kidney disease.

Liraglutide treatment also shows potential for nephroprotection by reducing albuminuria and slowing the decline in estimated glomerular filtration rate (eGFR) in certain subgroups of diabetic nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic Kidney Disease - Update 2018]. Ketteler, M., Wanner, C.[2019]

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]

In a study of 7,624 patients with chronic kidney disease (CKD), those using SGLT2 inhibitors, particularly dapagliflozin, showed a significantly lower risk of experiencing a decrease in estimated glomerular filtration rate (eGFR) by over 40% within one year.

SGLT2 inhibitor users also had a reduced rate of acute kidney injury (AKI)-related hospitalizations compared to non-users, indicating a potential safety benefit of these medications across various stages of CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal and Glucose-Lowering Effects of Empagliflozin and Dapagliflozin in Different Chronic Kidney Disease Stages. Lin, YH., Huang, YY., Hsieh, SH., et al.[2019]

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. sciencedirect.com sciencedirect.com/science/article/pii/S2589537025002706

Effects of empagliflozin on quality of life and healthcare use ... In EMPA-KIDNEY, 2 years of treatment with empagliflozin led to a small but measurable improvement in QALYs and lower costs for hospital admissions, concomitant ...

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

Guidelines - Chronic Kidney Disease | Jardiance Clinical Lower Limb Amputation: Lower limb amputations have been observed in patients with chronic kidney disease taking JARDIANCE. Peripheral artery disease, and ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39430801/?utm_source=Superfeedr%20bot&utm_medium=rss&utm_campaign=None&utm_content=1pEhTjOZGNUMUk_JTNAlPGlYt3NoTZjo_niSe_ODf-UlopnEpy&fc=None&ff=20241022190109&v=2.18.0.post9+e462414

Empagliflozin Use Is Associated With Lower Risk of All- ... Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06249945

Study Details | NCT06249945 | EMPAgliflozin in Heart ... The safety and efficacy of empagliflozin in patients with end-stage renal disease and heart failure with preserved ejection fraction - a randomized controlled ...