Effect of Canagliflozin on Ultrafiltration & Fibrosis in Patients on Peritoneal Dialysis

NCT ID: NCT06913647

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2028-09-30

Brief Summary

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.

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.

Conditions

ESRD; CKD (Chronic Kidney Disease) Stage 5D

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: ACTIVE_COMPARATOR

Canagliflozin 300 MG

Intervention Type: DRUG

Canagliflozin 300 mg once daily

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)

Group Type: PLACEBO_COMPARATOR

Canagliflozin 300 MG

Intervention Type: DRUG

Canagliflozin 300 mg once daily

Standard of care

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Canagliflozin 300 MG

Canagliflozin 300 mg once daily

Intervention Type: DRUG

Other Intervention Names

Invokana 300 mg

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

Thomas Mavrakanas

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas A. Mavrakanas, MD, MSc.

Role: PRINCIPAL_INVESTIGATOR

Research Institute-McGill University of Health Centre

Locations

Research Institute-McGill University Health Center

Montreal, Quebec, Canada

Countries

Canada

Central Contacts

Efrosyne Tsirella

Role: CONTACT

efrosyne.tsirella@muhc.mcgill.ca

514-934-1934 ext. 37836

Norka Rios

Role: CONTACT

norka.rios@muhc.mcgill.ca

514-934-1934 ext. 35207

Facility Contacts

Efrosyne Tsirella

Role: primary

efrosyne.tsirella@muhc.mcgill.ca

5149341934 ext. 37836

Norka Rios

Role: backup

norka.rios@muhc.mcgill.ca

514-934-1934 ext. 35207

Other Identifiers

2025-11346

Identifier Type: -

Identifier Source: org_study_id