Meg J Jardine1,2, Kenneth W Mahaffey3, Bruce Neal1,4,5,6, Rajiv Agarwal7, George L Bakris8, Barry M Brenner9, Scott Bull10, Christopher P Cannon11, David M Charytan12, Dick de Zeeuw13, Robert Edwards10, Tom Greene14, Hiddo J L Heerspink13, Adeera Levin15, Carol Pollock16, David C Wheeler17, John Xie10, Hong Zhang18, Bernard Zinman19, Mehul Desai10, Vlado Perkovic1. 1. The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia. 2. Concord Repatriation General Hospital and University of Sydney, Sydney, New South Wales, Australia. 3. Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. 4. The Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia. 5. Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. 6. Imperial College London, London, United Kingdom. 7. Indiana University School of Medicine and VA Medical Center, Indianapolis, Indiana, USA. 8. University of Chicago Medicine, Chicago, Illinois, USA. 9. Renal Division and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 10. Janssen Research & Development, LLC, Raritan, New Jersey, USA. 11. Cardiovascular Division, Brigham and Women's Hospital and Baim Institute for Clinical Research, Boston, Massachusetts, USA. 12. Renal Division, Brigham and Women's Hospital and Baim Institute for Clinical Research, Boston, Massachusetts, USA. 13. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 14. Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA. 15. Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada. 16. Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia. 17. Centre for Nephrology, UCL Medical School, London, United Kingdom. 18. Renal Division of Peking University First Hospital, Beijing, China. 19. Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND:People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitorslower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. METHODS: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin -versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to <90 mL/min/1.73 m2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. CONCLUSION: CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. TRIAL REGISTRATION: EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.
RCT Entities:
BACKGROUND:People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. METHODS: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin -versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to <90 mL/min/1.73 m2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. CONCLUSION: CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. TRIAL REGISTRATION: EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.
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