title: Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial.
abstract: The primary aim of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R) is to determine whether the favourable effects of inhibition of the sodium glucose co-transporter 2 (SGLT2) on blood glucose, blood pressure and body weight are accompanied by protection against adverse renal outcomes.
  
  
  
  CANVAS-R is a prospective, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes with a history or high risk of cardiovascular events. Patients were randomly assigned to once-daily placebo or canagliflozin 100 mg (with optional uptitration to 300 mg) for a planned average of 2.5 years of follow-up. The primary outcome is kidney disease progression, defined by class change in albuminuria. The two secondary outcomes are the composite of hospitalized heart failure or cardiovascular death, and cardiovascular death alone. Effects on end-stage renal disease and a range of other outcomes will also be explored.
  
  
  
  A total of 5812 participants were recruited at 422 sites in 24 countries between January 2014 and May 2015. The mean baseline age was 64 years, mean duration of diabetes was 14 years, mean glycated haemoglobin level was 8.3% and mean body mass index was 32 kg/m2. Of these participants, 37% were women, 71% had a history of cardiovascular disease, 22.3% had microalbuminuria and 8.7% had macroalbuminuria. The mean baseline estimated glomerular filtration rate was 76 mL/min/1.73 m2. The study will have at least 90% power ( P = .05) to detect a 22% or greater reduction in the risk of progression of albuminuria.
  
  
  
  The trial should define the potential renoprotective effect of canagliflozin and will provide additional important new data about its effects on vascular outcomes, death and kidney failure.
authors.affiliation: The George Institute for Global Health, Sydney, Australia.|The Charles Perkins Centre, University of Sydney, Sydney, Australia.|Royal Prince Alfred Hospital, Sydney, Australia.|Imperial College London, London, UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.affiliation: The George Institute for Global Health, Sydney, Australia.|The Royal North Shore Hospital, University of Sydney, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: University of Oxford, Oxford, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Matthews
authors.affiliation: Department of Medicine, Stanford Center for Clinical Research (SCCR), Stanford University, Stanford, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: The Royal North Shore Hospital, University of Sydney, Sydney, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Fulcher
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Ngozi
authors.initials: N
authors.lastname: Erondu
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Mehul
authors.initials: M
authors.lastname: Desai
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Wayne
authors.initials: W
authors.lastname: Shaw
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Vercruysse
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Yee
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Hsiaowei
authors.initials: H
authors.lastname: Deng
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
mesh_terms: D000368:Aged; D000419:Albuminuria; D001786:Blood Glucose; D001794:Blood Pressure; D001835:Body Weight; D000068896:Canagliflozin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000378:metabolism*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin
keywords: 
  SGLT2 inhibitor; cardiovascular disease; type 2 diabetes