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

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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 &lt;90 mL/min/1.73 m², and albuminuria (urinary albumin:creatinine ratio &gt;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. <b><i>Conclusion:</i></b> 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. <b><i>Trial Registration:</i></b> EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.

<b><i>背景：</i></b> 糖尿病合并确诊肾病患者发生心血管事件及肾病进展的风险极高。钠-葡萄糖协同转运蛋白2抑制剂（Sodium glucose co-transporter 2 inhibitors）通过减少肾小管对滤过葡萄糖的重吸收来降低血浆葡萄糖水平，进而增加尿糖排泄。已有多项研究证实，此类药物可在2型糖尿病患者中诱导轻度排钠利尿，并降低糖化血红蛋白（HbA1c）水平、血压、体重及白蛋白尿。然而，此类药物对2型糖尿病合并确诊肾病患者的肾脏及心血管事件的影响，尚未得到充分研究。
<b><i>方法：</i></b> 糖尿病合并确诊肾病患者的卡格列净与肾脏终点临床评估试验（Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation, CREDENCE）旨在对比卡格列净与安慰剂在预防糖尿病合并确诊肾病患者发生临床意义重大的肾脏及心血管结局方面的有效性与安全性。该试验为随机、双盲、事件驱动型安慰剂对照试验，在34个国家开展，预计持续时长约5.5年，计划纳入4401名2型糖尿病成人患者，其估算肾小球滤过率（estimated glomerular filtration rate, eGFR）≥30且<90 mL/min/1.73 m²，同时存在白蛋白尿（尿白蛋白肌酐比（urinary albumin:creatinine ratio, UACR）>300且≤5000 mg/g）。本试验具有90%的检验效能，可检测出主要终点风险降低20%的差异（检验水准α=0.05）；主要终点为复合终点，包括终末期肾病、血清肌酐翻倍以及肾脏或心血管死亡。
<b><i>结论：</i></b> 本试验将为卡格列净对2型糖尿病合并确诊肾病患者的肾脏（及心血管）结局的影响提供确凿证据。
<b><i>试验注册：</i></b> 欧盟临床试验注册系统（EudraCT）编号：2013-004494-28；临床试验.gov（ClinicalTrials.gov）标识符：NCT02065791。