Empagliflozin for Kidney Disease

(EMPA-PD Trial)

Overseen By Kara Otis

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

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

Compensation: Varies

Number of Visits: 5

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if empagliflozin (Jardiance), a medication used to lower blood sugar, can reduce sugar absorption through the abdominal lining (peritoneal glucose absorption) in individuals with severe kidney disease on peritoneal dialysis. Participants will receive either empagliflozin or a placebo (a non-active pill) to compare effects. This trial is especially suited for those who have been on stable peritoneal dialysis for over three months and have no history of type 1 diabetes or recent serious infections. As a Phase 4 trial, this research explores how an FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you cannot have used an SGLT2 inhibitor in the last 30 days.

What is the safety track record for empagliflozin?

Studies have shown that empagliflozin is generally safe for people with kidney disease. Research indicates that it lowers the risk of kidney failure and heart-related deaths compared to a placebo. In people with type 2 diabetes and advanced chronic kidney disease (CKD), no new safety concerns emerged.

Regarding side effects, data shows that empagliflozin reduces the risk of serious sudden kidney problems compared to a placebo. Evidence also suggests it lowers the chance of large increases in blood markers like serum creatinine, which are often linked to kidney issues.

Overall, these findings suggest that empagliflozin is well-tolerated and safe for people with kidney problems. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike traditional treatments for chronic kidney disease that mainly focus on controlling symptoms and slowing disease progression, empagliflozin offers a unique approach by targeting the SGLT2 protein in the kidneys. This mechanism helps to reduce blood sugar levels and may also protect kidney function. Researchers are excited about empagliflozin because it not only aids in managing blood sugar but has shown potential in reducing the risk of kidney disease progression and cardiovascular events, which are common in patients with kidney issues. The possibility of a dual benefit for both kidney and heart health makes empagliflozin a promising option in the treatment landscape.

What is the effectiveness track record for empagliflozin in reducing peritoneal glucose absorption in patients with end stage renal disease?

Research shows that empagliflozin can help slow chronic kidney disease (CKD). One study found that empagliflozin lowered the risk of worsening kidney disease or death from heart-related issues. People with CKD who used empagliflozin experienced slower disease progression. In this trial, participants in the chronic phase will receive empagliflozin to assess its effects over 8 weeks. For sudden kidney problems, the trial will evaluate empagliflozin in an acute phase, where participants will receive either empagliflozin or a placebo. Previous studies have shown that empagliflozin and similar treatments reduced the risk of acute kidney injury by up to 28%. These findings suggest that empagliflozin may benefit kidney health in various situations. ^{1 6 7 8 9}

Who Is on the Research Team?

Jeffrey Testani, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with end stage renal disease on peritoneal dialysis, who have been on a stable dialysis prescription for more than 3 months and produce at least 400 ml of urine daily. It's not suitable for those with type 1 diabetes, recent severe hypoglycemia, or infections related to their dialysis catheter.

Inclusion Criteria

You have been diagnosed with Parkinson's disease for more than 3 months.

My peritoneal dialysis treatment plan hasn't changed recently.

I am on long-term water pills for my condition.

Exclusion Criteria

I have had peritonitis or an infection in my dialysis catheter recently.

I have taken an SGLT2 inhibitor in the last 30 days.

Your hemoglobin level is less than 8 grams per deciliter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Treatment

Participants receive 25 mg empagliflozin or placebo once, with crossover to the alternate treatment after one week

1 week

2 visits (in-person)

Chronic Treatment

All participants receive 10 mg empagliflozin daily for 8 weeks

8 weeks

3 study visits and up to 4 safety 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

Trial Overview

The study tests if Empagliflozin can lower glucose absorption in patients undergoing peritoneal dialysis. Participants will either receive Empagliflozin or a placebo in a randomized manner, followed by an open label phase where all get the drug.

How Is the Trial Designed?

Group I: Empagliflozin or Placebo in Acute Experimental Treatment 1 Intervention

Acute phase: Participants will receive 25 mg empagliflozin once on Day 0 or Day 7. Participants receive empaglifozin or placebo on Day 0. On Day 7, they will be crossed over to the alternate treatment.

Group II: Empagliflozin in Chronic Active Control 1 Intervention

Chronic phase: On day 8, all participants will receive 10 mg empagliflozin 10 mg x 8 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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

In the EMPA-KIDNEY trial involving 6609 participants, empagliflozin significantly slowed the progression of chronic kidney disease, reducing the chronic decline in kidney function by 50% after an initial dip in eGFR.

The benefits of empagliflozin were observed across various patient groups, indicating that albuminuria levels should not be the sole factor in deciding treatment with SGLT2 inhibitors, as even patients with low albuminuria experienced significant improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

In a study of 26,347 Asian patients with chronic kidney disease (CKD) and diabetes, empagliflozin significantly reduced major adverse cardiac events (MACEs), all-cause mortality, and other serious health issues compared to sitagliptin.

While empagliflozin showed overall safety and efficacy benefits, it was associated with a higher risk of genital tract infections, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Safety Analysis of Empagliflozin in Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease versus Normal Kidney Function: A Nationwide Cohort Study in Korea. Jang, HY., Kim, IW., Oh, JM.[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]

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 (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 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 (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]

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 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]

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an individual participant-level meta-analysis

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nejm.org

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Empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo.

8.

pmc.ncbi.nlm.nih.gov

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We found that empagliflozin reduced the risk of those large serum creatinine increases by 20%, and reduced AKI adverse events by 27%. These ...