The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics.
Publication/Presentation Date
12-13-2017
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 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/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.
Volume
46
Issue
6
First Page
462
Last Page
472
ISSN
1421-9670
Published In/Presented At
Jardine, M. J., Mahaffey, K. W., Neal, B., Agarwal, R., Bakris, G. L., Brenner, B. M., Bull, S., Cannon, C. P., Charytan, D. M., de Zeeuw, D., Edwards, R., Greene, T., Heerspink, H. J. L., Levin, A., Pollock, C., Wheeler, D. C., Xie, J., Zhang, H., Zinman, B., Desai, M., … CREDENCE study investigators (2017). The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics. American journal of nephrology, 46(6), 462–472. Advance online publication. https://doi.org/10.1159/000484633
Disciplines
Medicine and Health Sciences
PubMedID
29253846
Department(s)
Department of Medicine
Document Type
Article