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

Trial Summary

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.

What data supports the effectiveness of the drug empagliflozin for kidney disease?

Empagliflozin has been shown to reduce the progression of chronic kidney disease and lower the risk of cardiovascular issues in patients with type 2 diabetes and established cardiovascular disease. In the EMPA-REG Outcome trial, it significantly reduced the risk of cardiovascular death, hospitalization for heart failure, and worsening kidney problems. ^{1 2 3 4 5}

Is empagliflozin safe for people with kidney disease?

Empagliflozin (Jardiance) is generally considered safe for people, including those with chronic kidney disease (CKD), but it can have side effects like fluid deficits. It has been studied in various conditions, showing benefits for heart and kidney health, but patients should be monitored for any adverse effects. ^{5 6 7 8 9}

How does the drug empagliflozin differ from other treatments for kidney disease?

Empagliflozin is unique because it is a sodium-glucose co-transporter-2 (SGLT2) inhibitor that not only helps manage blood sugar levels in type 2 diabetes but also offers kidney and heart protection, reducing the progression of chronic kidney disease and cardiovascular risks. Unlike some other treatments, it works independently of insulin and can lower blood pressure and body weight, making it a multifaceted option for patients with kidney disease. ^{2 4 5 7 10}

What is the purpose of this trial?

The primary aim of this study is to determine the safety and mechanisms of SGLT2 inhibition in individuals on peritoneal dialysis (PD) with residual kidney function (RKF).

Research Team

Sunita KS Singh, MD MSc FRCPC

Principal Investigator

University Health Network, Toronto General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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-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 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]

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]

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 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]

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]

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]

References

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

Empagliflozin in Patients with Chronic Kidney Disease. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

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]

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

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. [2022]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Switzerland 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. [2023]

9. 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]

10. Belgium pubmed.ncbi.nlm.nih.gov

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