Abstract 18957: Rationale, Design, and Analysis of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R) - A Randomized, Placebo-Controlled Trial
Introduction: Inhibitors of sodium glucose co-transporter 2 (SGLT2) have been approved to treat patients with type 2 diabetes mellitus (T2DM), and the first large outcome trial to report on SGLT2 inhibitors demonstrated cardiovascular protection.
Hypothesis: The CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R) will test the effects of canagliflozin compared to placebo on the risk of kidney disease progression but will also provide substantial new insight into the effects of SGLT2 inhibition on vascular outcomes.
Methods: CANVAS-R is a prospective, randomized, double-blind, placebo-controlled clinical trial that has randomized 5,812 patients with T2DM (HbA1c ≥7.0% and ≤10.5%) with a history or high risk of cardiovascular events (ClinicalTrials.gov, NCT01989754). Patients have been assigned (1:1) to once-daily placebo or canagliflozin 100 mg (with optional up-titration to 300 mg) for a planned average of 2.5 years follow-up. The primary outcome will be progression of albuminuria, for which the study has at least 90% power (α = 5%) to detect a 22% or greater reduction in risk. In conjunction with the CANVAS trial, there will be about 870 major adverse cardiovascular events accrued by trial completion, which will provide at least 80% power (α = 5%) to detect a risk reduction of 19% or greater.
Results: Recruitment was completed in May 2015. Mean baseline age was 64 years, duration of diabetes was 14 years; HbA1c was 8.3%, and body mass index was 32 kg/m2. Participants are 37% female, and about 70% had a history of atherosclerotic cardiovascular disease. The trial is anticipated to complete follow-up in 2017 and report results shortly thereafter.
Conclusions: CANVAS-R should clearly define the effect of canagliflozin on progression of albuminuria. In conjunction with the ongoing CANVAS trial, this study will also enable the post-marketing evaluation of the cardiovascular safety and efficacy of canagliflozin and add substantially to the evidence base describing the effects of SGLT2 inhibition on vascular outcomes.
Author Disclosures: D. de Zeeuw: Consultant/Advisory Board; Modest; AbbVie, Astellas, Chemocentryx, Eli Lilly, Fresenius, Janssen and Merck Darmstadt; all consultancy honoraria are paid to his institution. B. Neal: Research Grant; Modest; Janssen and for other large-scale cardiovascular outcome trials from Roche, Servier and Merck Schering Plough. Honoraria; Modest; Abbott, Novartis, Pfizer, Roche and Servier for contributions to the continuing medical education programmes. Other; Modest; Supported by a National Health and Medical Research Council Senior Research Fellowship. V. Perkovic: Consultant/Advisory Board; Modest; Janssen, Baxter, AbbVie, Astellas, Boehringer Ingelheim, AstraZeneca, Eli Lilly, Merck and GlaxoSmithKline. Other; Modest; supported by a Senior Research Fellowship from the Australian National Health and Medical Research Council. K.W. Mahaffey: Research Grant; Significant; Amgen, Daiichi-Sankyo, Johnson & Johnson, Medtronic, Merck, St Jude, Tenax. Consultant/Advisory Board; Modest; BAROnova, BI, Bio2 Medical, Epson, Eli Lilly, Johnson & Johnson, Myokardia, Portola, BMS, GSK, Theravance. Consultant/Advisory Board; Significant; AstraZeneca, Cubist, Merck, The Medicines Company. Other; Modest; All disclosures after August 1, 2013, can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. G. Fulcher: Consultant/Advisory Board; Modest; advisory boards for Johnson & Johnson, consultant to Janssen. M. Desai: Employment; Significant; Janssen Research & Development, LLC. J. Yee: Employment; Significant; Janssen Research & Development, LLC. W. Shaw: Employment; Significant; Janssen Research & Development, LLC. H. Deng: Employment; Significant; Janssen Research & Development, LLC. E. Fabbrini: Employment; Significant; Janssen Research & Development, LLC. F. Vercruysse: Employment; Significant; Janssen Research & Development. N. Erondu: Employment; Significant; Janssen Research & Development, LLC. D. Matthews: Research Grant; Modest; Janssen and NIHR. Speakers Bureau; Modest; Novo Nordisk, Servier, Sanofi-Aventis, Eli Lilly, Novartis, Janssen and Aché Laboratories. Consultant/Advisory Board; Modest; Novo Nordisk, GlaxoSmithKline, Novartis, Eli Lilly, Sanofi-Aventis, Janssen and Servier.
- © 2016 by American Heart Association, Inc.