Empagliflozin for Kidney Disease

(CANARY Trial)

Overseen By Vesta Lai

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Health Network, Toronto

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Organ transplant, Pregnancy, Alcohol or drug abuse, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 2 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called empagliflozin to evaluate its safety and effectiveness for people with kidney disease who are on peritoneal dialysis but still retain some kidney function. The focus is on understanding the drug's impact on kidney function and overall health. Suitable participants have been on stable peritoneal dialysis and produce at least 250 cc of urine daily. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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

The trial does not specify if you need to stop your current medications, but you must have a stable dose of RAAS blockade if you are on this type of medication. You also cannot have used an SGLT2 inhibitor in the 30 days before the trial.

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

Previous studies have shown that empagliflozin is safe for people with chronic kidney disease. Research indicates that empagliflozin can lower the risk of worsening kidney problems and reduce the chance of dying from heart-related issues. Serious side effects, such as urinary tract infections, were rare, occurring in only 1.6% of patients.

For those with type 2 diabetes and advanced chronic kidney disease, empagliflozin did not present new safety concerns and might even support kidney health. As this trial is in a later stage, earlier studies have likely addressed any major safety issues, providing some confidence about its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for kidney disease focus on managing symptoms and slowing progression, usually involving blood pressure medications or dialysis. But empagliflozin works differently, targeting sodium-glucose co-transporter 2 (SGLT2) in the kidneys. This mechanism not only helps control blood sugar levels but also reduces the risk of kidney damage by decreasing pressure in the kidney's filtering units. Researchers are excited about empagliflozin because it has shown promise in protecting kidney function, offering a potential dual benefit for patients with kidney disease, especially those with diabetes.

What evidence suggests that Empagliflozin might be an effective treatment for kidney disease?

Research has shown that empagliflozin, which participants in this trial will receive, can help slow chronic kidney disease (CKD). One study found that it reduced the risk of disease progression or death from heart problems. Another study demonstrated that empagliflozin slowed CKD progression, even in individuals with only a small amount of protein in their urine. These findings suggest that empagliflozin might benefit people with kidney issues. ^{1 6 7 8 9}

Who Is on the Research Team?

Sunita KS Singh, MD MSc FRCPC

Principal Investigator

University Health Network, Toronto General Hospital

Are You a Good Fit for This Trial?

Adults over 18 on peritoneal dialysis with some remaining kidney function, specifically at least 250 cc of daily urine output and a minimum GFR of 2 ml/min/1.73m^2. Participants must not have had recent organ transplants, be pregnant or nursing, have type 1 diabetes, recent heart or stroke events, drug abuse issues, or any condition that could affect safety or results as judged by the trial investigator.

Inclusion Criteria

My peritoneal dialysis prescription hasn't changed recently.

My RAAS blocker dose has been the same for the last 30 days.

Signed and dated written informed consent.

Exclusion Criteria

I am scheduled for surgery or tests needing dye during the trial.

I have Type 1 diabetes.

You have had problems with alcohol or drugs in the past 3 months that could affect your ability to take part in the trial, as decided by the doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 25mg of Empagliflozin daily to evaluate safety and efficacy in patients on peritoneal dialysis with residual kidney function

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a GFR measurement 2 weeks after cessation of therapy

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview

The study is testing the safety and how well Empagliflozin (25 MG), an SGLT2 inhibitor medication typically used for diabetes management, works in patients undergoing peritoneal dialysis who still retain some kidney function.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

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 Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

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]

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 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]

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]

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 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 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]

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]

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]

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]

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 ...

Probabilities of empagliflozin being cost-effective over 2 years were 43% and 61% and over 4 years were 91% and 94% at willingness to pay thresholds of £20,000 ...

4.

pro.boehringer-ingelheim.com

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

Guidelines - Chronic Kidney Disease | Jardiance Clinical

Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including JARDIANCE.

5.

jacc.org

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

Efficacy of Empagliflozin in Patients With Heart Failure ...

Empagliflozin reduced the risk of cardiovascular death or hospitalizations for HF similarly in all Kidney Disease Improving Global Outcomes ( ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7614055/

Empagliflozin in Patients with Chronic Kidney Disease - PMC

Empagliflozin reduced the risk of the composite outcome of kidney disease ... Safety outcomes. Serious urinary tract infection, 52, (1.6%), 0.81 ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2213858723003224

Articles Impact of primary kidney disease on the effects ...

The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in ...

8.

pro.boehringer-ingelheim.com

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

Safety Profile for CKD | Jardiance® (empagliflozin) tablets

See the JARDIANCE safety profile in the EMPA-KIDNEY trial for adult patients with chronic kidney disease. View Safety, PI and Med Guide.

9.

diabetesjournals.org

diabetesjournals.org/care/article/45/6/1445/145036/Safety-of-Empagliflozin-in-Patients-With-Type-2

Safety of Empagliflozin in Patients With Type 2 Diabetes and ...

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 ...