The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics

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 <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.

Keywords: Canagliflozin; Chronic kidney disease; Diabetic nephropathy; Renal outcomes.

© 2017 S. Karger AG, Basel.

Figures

Fig. 1.

Study design. eGFR, estimated glomerular filtration rate; AHA, anti-hyperglycemic agent; BP, blood pressure; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; HbA1c, glycated hemoglobin; R, randomization; FPI, first patient in; Wk, week; UACR, urinary albumin:creatinine ratio.

Fig. 2.

Overview of trial timelines. CANVAS, CANagliflozin cardioVascular Assessment Study; T2DM, type 2 diabetes mellitus; CVD, cardiovascular disease; CANVAS-R, CANagliflozin cardioVascular Assessment Study–Renal; EMPA-REG, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; ­CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; DKD, diabetic kidney disease; GFR, glomerular filtration rate; CKD, chronic kidney disease. * Note that the patient populations in CANVAS and CANVAS-R are nearly identical to facilitate an integrated analysis of the data.