Effects of canagliflozin on brain natriuretic peptide levels in patients with type 2 diabetes on peritoneal dialysis in Japan: protocol for a multicentre, prospective, randomised controlled trial (CARD-PD trial)

INTRODUCTION: Patients with type 2 diabetes (T2D) undergoing dialysis exhibit a higher mortality rate compared with those with other conditions, primarily due to vascular complications including coronary artery disease, heart failure and stroke. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a type of drug for T2D, have reportedly decreased cardiovascular and renal events in patients with heart failure and chronic kidney disease, irrespective of diabetes presence. Nevertheless, the evidence supporting the use of SGLT2 inhibitors in patients undergoing dialysis has been limited. Our study aims to evaluate the impact of SGLT2 inhibitors on cardiovascular disease in individuals with T2D undergoing peritoneal dialysis (PD). METHODS AND ANALYSIS: The CARD-PD study is a multicentre, prospective, randomised, open-label comparison trial of canagliflozin treatment in patients diagnosed with T2D undergoing PD. Eligible patients meeting the criteria for participation will be randomly assigned to either the canagliflozin treatment group (100 mg/day) or the control group (delayed-start canagliflozin group) for a duration of 6 months. We set a target of 18 participants in each group (a total of 36) based on sample size calculations from a previous report. Randomisation is performed using a web-based system, wherein patients are stratified by age, sex and plasma brain natriuretic peptide (BNP) concentrations at the baseline. The primary outcome measure is the plasma BNP levels after 6-month period. Following this initial phase, patients from both groups will continue to receive canagliflozin treatment (100 mg/day) in the following manner: (1) patients in the canagliflozin group will continue canagliflozin treatment for an additional 6 months, while (2) patients initially in the placebo arm will transition to canagliflozin treatment for an additional 12 months. ETHICS AND DISSEMINATION: The Ethics Review Board of Hokkaido University Hospital (CRB no. 1180001) has approved the CARD-PD study protocol. The results will be disseminated in peer-reviewed journals and summaries will be presented at scientific conferences. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT1011210022); pre-results.