Effect of Canagliflozin on Ultrafiltration & Fibrosis in Patients on Peritoneal Dialysis (CAN-PD)

Effect of Canagliflozin on Ultrafiltration and Fibrosis in Peritoneal Dialysis: a a Proof-of-concept Randomized Phase II Crossover Clinical Trial

This is a phase II, proof-of-concept, placebo-controlled, double-blind, cross-over randomized clinical trial, assessing the effect of canagliflozin on peritoneal membrane function in patients on PD.

The primary aim of this trial is to determine the short-term effects of canagliflozin, an SGLT-2 inhibitor, on glucose absorption by the peritoneal membrane and on ultrafiltration, as assessed by a standardized peritoneal equilibrium test. The secondary aims are to determine the effect of canagliflozin on solute clearance and on effluent biomarkers of inflammation, angiogenesis, and fibrosis at 26 weeks. We hypothesize that canagliflozin will prevent glucose absorption by the peritoneal membrane, as compared with placebo, and will attenuate the development of inflammation, angiogenesis, and fibrosis of the peritoneal membrane, as assessed by relevant biomarkers in the dialysate.

Study Overview

• Status: Recruiting
• Conditions: ESRD; CKD (Chronic Kidney Disease) Stage 5D
• Intervention / Treatment: Drug: Canagliflozin 300 MG

Detailed Description

Patients with kidney failure on peritoneal dialysis who meet the study inclusion criteria will be randomized at a 2:2:1 ratio to one of the following arms:

(i) 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).

(ii) 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).

(iii) standard of care, with no active treatment, for 26 weeks (open label). Four in-person and one phone study visits have been scheduled: baseline visit, week 5, week 10, week 18 (phone visit), and week 26. A standardized peritoneal equilibration test (PET) will be performed at each of the in-person visits. There will also be two safety assessments at weeks 2 and 7, which will consist of blood tests. Patients who develop intercurrent illnesses or are hospitalized may temporarily discontinue the study drug if deemed appropriate by the treating physician.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Efrosyne Tsirella; Phone Number: 37836 514-934-1934; Email: efrosyne.tsirella@muhc.mcgill.ca
• Study Contact Backup: Name: Norka Rios; Phone Number: 35207 514-934-1934; Email: norka.rios@muhc.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Recruiting
      • Research Institute-McGill University Health Center
      • Contact: Norka Rios; Phone Number: 35207 514-934-1934; Email: norka.rios@muhc.mcgill.ca
      • Contact: Efrosyne Tsirella; Phone Number: 37836 5149341934; Email: efrosyne.tsirella@muhc.mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients with kidney failure on PD (both incident and prevalent) who are on a stable prescription of dextrose-based solutions for at least 3 months.
• Only high or high-average transporters, as classified by PET, will be included.

Exclusion Criteria:

• History of euglycemic ketoacidosis
• Known hypersensitivity to canagliflozin
• Active peritonitis or tunnel infection
• Kidney transplant scheduled in the next 6 months
• Severe liver cirrhosis (Child-Pugh class C stage)
• Recurrent severe genital or urine infections
• Patients receiving digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if these agents cannot be safely discontinued
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active treatment followed by placebo; 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)	Drug: Canagliflozin 300 MG; Canagliflozin 300 mg once daily; Other Names: Invokana 300 mg
Placebo Comparator: Placebo followed by active treatment; 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)	Drug: Canagliflozin 300 MG; Canagliflozin 300 mg once daily; Other Names: Invokana 300 mg
No Intervention: Standard of care; Standard of care, with no active treatment, for 26 weeks (open label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in D4/D0	Change in the ratio of intraperitoneal glucose at 0 and 4h post infusion (D4/D0 ratio) in a standardized PET with canagliflozin, compared with placebo.	5 and 10 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ultrafiltration	Change in ultrafiltration, as assessed by the volume of drain after a 4h dwell with 2 L of a 2.5% dextrose solution minus the volume infused, with canagliflozin compared with placebo.	5 and10 weeks from baseline
Change in sodium dip/ sieving	Change in sodium dip/ sieving, calculated as the absolute difference in dialysate sodium at 0 and 1h post infusion in a standardized PET, with canagliflozin compared with placebo.	5 and 10 weeks from baseline
Change in small solute clearance	Change in small solute clearance, as assessed by the dialysate-to-plasma (D/P) creatinine and urea at the end of a 4h-dwell, with canagliflozin compared with placebo.	5 and10 weeks from baseline
Canagliflozin levels in the dialysate	Canagliflozin levels in the dialysate at 5 and 10 weeks, as assessed by mass spectrometry	5 and10 weeks from baseline
Change in small and middle solute clearance	Change in small and middle solute clearance using weekly Kt/V urea, weekly creatinine clearance, clearance of β2-microglobulin, and modifications in PD prescription.	26 weeks from baseline
Change in effluent biomarker levels	Change in effluent biomarker levels at 26 weeks from baseline. The panel of biomarkers includes interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), cancer antigen-125 (CA-125), plasminogen activator inhibitor-1 (PAI-1), and decoy recptor-2 (eDcR2), assessed by using enzyme-linked colorimetric immunoassays.	26 weeks from baseline
Change in residual kidney function	Change in residual kidney function, as assessed by the 24h urine output and 24h native urea and creatinine clearance	26 weeks from baseline
Change in blood pressure	Change in 24h-ambulatory blood pressure measurements at 26 weeks from baseline	26 weeks from baseline
6-minute walk test	Change in distance in the 6-minute walk test at 26 weeks from baseline	26 weeks from baseline
Change in dyspnea score	Change in dyspnea score using the 7-point Likert scale and Visual analog scale questionnaire at 26 weeks from baseline	26 weeks from baseline
Change in quality of life	Difference in quality of life using the Kidney Disease Quality of Life questionnaire at 26 weeks from baseline	26 weeks from baseline
Major adverse cardiovascular events	Composite of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure	26 weeks from baseline
Death from any cause	Death from any cause	26 weeks from baseline
Safety outcomes	Safety outcomes, including serious adverse events and any adverse events	26 weeks from baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility outcome	Ability to recruit for the study at the anticipated average recruitment rate and study completion with at least 80% adherence with reasons for non-adherence being reported	26 weeks from baseline

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Thomas A. Mavrakanas, MD, MSc., Research Institute-McGill University of Health Centre

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Canagliflozin; Peritoneal dialysis; Ultrafiltration failure; SGLT-2 inhibitors; Peritoneal fibrosis
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Digestive System Diseases; Renal Insufficiency; Peritoneal Diseases; Fibrosis; Pathological Conditions, Signs and Symptoms; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Peritoneal Fibrosis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates; Glucosides; Glycosides; Thiophenes; Canagliflozin
• Other Study ID Numbers: 2025-11346

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: An anonymized dataset may be shared with other investigators in the future after the publication of primary results of this clinical trial. Any request for data sharing will have to be approved by the clinical trial steering committee after having examined the data sharing proposal. A data use agreement will be required through the Contracts Office of the Research Institute of McGill University Health Center.
• IPD Sharing Time Frame: The data may become available twelve months after the end of the study.
• IPD Sharing Access Criteria: Any request for data sharing will have to be approved by the clinical trial steering committee after having examined the data sharing proposal. A data use agreement will be required through the Contracts Office of the Research Institute of McGill University Health Center.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No