Canagliflozin for Chronic Kidney Disease

(CAN-PD Trial)

Overseen By Norka Rios

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Digoxin, Phenobarbital, Phenytoin, others

Disqualifiers: Euglycemic ketoacidosis, Severe liver cirrhosis, others

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

Compensation: Varies

Number of Visits: 5

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of canagliflozin, a medication used to lower blood sugar levels, on individuals with kidney failure undergoing peritoneal dialysis (PD). PD uses a special fluid to clean the blood inside the body. The researchers aim to determine if canagliflozin can reduce sugar absorption in the peritoneal membrane, improve waste removal, and decrease inflammation and other complications. Participants will receive either canagliflozin or a placebo in different sequences to compare effects. This trial may suit those who have maintained stable PD treatment for at least three months and are classified as high or high-average transporters by a specific test. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if they cannot be safely discontinued. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that canagliflozin is generally safe for people. Studies have found it reduces the risk of kidney failure and heart problems, particularly in those with type 2 diabetes and chronic kidney disease. Canagliflozin is also safe for various age groups, including older adults, without additional safety concerns.

In these studies, most participants tolerated canagliflozin well, and no major safety issues were reported. While side effects may occur, research suggests that canagliflozin is safe for many. Always discuss any treatment concerns with a doctor. ^{1 2 3 4 5}

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

Canagliflozin is unique because it targets the kidneys differently from traditional treatments like ACE inhibitors or ARBs. While those standard treatments mainly manage blood pressure and protein levels, Canagliflozin works by promoting sugar excretion through urine, which may help protect kidney function. Researchers are excited about this drug because it offers a new way to potentially slow down kidney damage in people with chronic kidney disease, providing hope for improved outcomes.

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

Studies have shown that canagliflozin effectively treats long-term kidney disease, especially in individuals with type 2 diabetes. Research indicates that this drug lowers the risk of serious kidney problems and slows kidney damage. In this trial, participants may receive canagliflozin, which previous studies have shown results in fewer kidney failures compared to those who did not take it. Additionally, canagliflozin helps protect the kidneys by reducing the chance of reaching the most severe stage of kidney disease. Overall, strong evidence supports canagliflozin's ability to improve kidney health in people with ongoing kidney issues. ^{2 6 7 8 9}

Who Is on the Research Team?

Thomas A. Mavrakanas, MD, MSc.

Principal Investigator

Research Institute-McGill University of Health Centre

Are You a Good Fit for This Trial?

This trial is for patients on peritoneal dialysis who may have conditions like chronic kidney disease or renal disease. Participants should not have contrast-induced nephropathy or thyroid fibrosis. The study seeks individuals to test the effects of a drug called Canagliflozin.

Inclusion Criteria

I have kidney failure, am on PD, and have used dextrose-based solutions for 3+ months.

Only high or high-average transporters, as classified by PET, will be included

Exclusion Criteria

Pregnancy or breastfeeding

I have had ketoacidosis with normal blood sugar levels before.

Known hypersensitivity to canagliflozin

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive canagliflozin or placebo for 5 weeks, followed by crossover to the alternate treatment for another 5 weeks, and then canagliflozin for 16 weeks

26 weeks

4 visits (in-person), 1 visit (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Canagliflozin

Trial Overview

The trial tests Canagliflozin, an SGLT-2 inhibitor, against a placebo to see if it affects glucose absorption and ultrafiltration in the peritoneum. It's double-blind and cross-over, meaning neither doctors nor patients know who gets the real drug at first, then they switch.

How Is the Trial Designed?

Group I: Active treatment followed by placebo Active Control 1 Intervention

Canagliflozin 300 mg once daily for 5 weeks (double-blind), followed by matching placebo once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 16 weeks (open label)

Group II: Standard of care Active Control 1 Intervention

Standard of care, with no active treatment, for 26 weeks (open label)

Group III: Placebo followed by active treatment Placebo Group 1 Intervention

Placebo once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 16 weeks (open label)

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Canagliflozin significantly improved glycemic control in patients with type 2 diabetes and stage 3 chronic kidney disease, reducing HbA1c levels compared to placebo after 26 weeks.

The treatment was generally well tolerated, with similar rates of adverse events compared to placebo, although there were slightly higher instances of urinary tract infections and other osmotic diuresis-related effects at the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Yale, JF., Bakris, G., Cariou, B., et al.[2022]

Canagliflozin significantly reduces the risk of cardiovascular events and kidney outcomes in individuals with type 2 diabetes, showing a consistent relative effect across different KDIGO risk categories based on kidney function and albumin levels.

Higher KDIGO risk categories experienced greater absolute reductions in cardiovascular outcomes, suggesting that patients with more severe kidney disease may benefit more from canagliflozin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Neuen, BL., Ohkuma, T., Neal, B., et al.[2021]

Canagliflozin, an SGLT-2 inhibitor, showed potential in improving kidney function in rats with non-diabetic chronic kidney disease (CKD) induced by adenine, significantly reducing inflammation and oxidative stress markers.

The drug did not cause any significant adverse effects, suggesting it may be safe for further investigation in human trials for CKD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats. Ali, BH., Al Salam, S., Al Suleimani, Y., et al.[2020]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1811744

Canagliflozin and Renal Outcomes in Type 2 Diabetes and ...

In this trial, we found that patients with type 2 diabetes and chronic kidney disease who received canagliflozin had a lower risk of the primary composite ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6181277/

Cardiovascular and Renal Outcomes With Canagliflozin ...

The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55–0.90) and those with ...

3.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.042007

Canagliflozin and Cardiovascular and Renal Outcomes in ...

Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2590059524000621

SGLT2 Inhibitor Use in Chronic Kidney Disease

In 2020, canagliflozin was approved by the US Food and Drug Administration (FDA) to reduce the risk of end-stage kidney disease, doubling of serum creatinine ...

5.

kidney-international.org

kidney-international.org/article/S0085-2538%2824%2900625-2/fulltext

A randomized, open-label, clinical trial examined the ...

Canagliflozin treatment resulted in a statistically significant effect in slowing the patient-specific natural course of eGFR decline in ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7217416/

Renal, Cardiovascular, and Safety Outcomes of Canagliflozin ...

Canagliflozin safely reduced the risk of renal and cardiovascular events, with consistent results across eGFR subgroups, including the subgroup initiating ...

7.

diabetesjournals.org

diabetesjournals.org/care/article/47/3/501/154163/Impact-of-Canagliflozin-on-Kidney-and

Impact of Canagliflozin on Kidney and Cardiovascular ...

Our findings suggest that earlier treatment with canagliflozin confers consistent cardiorenal benefits to individuals with type 2 diabetes.

8.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.035901

Cardiovascular and Renal Outcomes With Canagliflozin ...

The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55–0.90) ...

9.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39781601/

A combined analysis from the CANVAS Program and ...

Canagliflozin reduced cardiovascular and kidney outcomes, regardless of age, with no additional safety concerns identified in older patients.