Duke University School of Medicine and Duke Clinical Research Institute, Durham, NC, USA.
Division of Nephrology and Hypertension, University of North Carolina Kidney Center, UNC School of Medicine, Chapel Hill, NC, USA.
Nephrol Dial Transplant. 2023 Mar 31;38(4):894-903. doi: 10.1093/ndt/gfac198.
Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone.
CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a urine albumin:creatinine ratio (UACR) ≥300-<5000 mg/g. The primary objective is to demonstrate that 6 months of dual therapy comprising finerenone and the SGLT2i empagliflozin is superior for reducing albuminuria versus either agent alone. Interventions will be once-daily finerenone 10 mg or 20 mg (target dose) plus empagliflozin 10 mg, or empagliflozin 10 mg alone, or finerenone 10 mg or 20 mg (target dose) alone.
The primary outcome is a relative change from baseline in UACR among the three groups. Secondary outcomes will further characterize efficacy and safety, including changes in estimated glomerular filtration rate and incident hyperkalemia.
CONFIDENCE is evaluating the safety, tolerability and efficacy of dual use of finerenone and an SGLT2i in adults with CKD and T2D. Should an additive effect be shown, early and efficient intervention with dual finerenone and SGLT2i therapy could slow disease progression and provide long-term benefits for people with CKD and T2D.
尽管有可用的干预措施，2 型糖尿病（T2D）患者仍然存在慢性肾脏病（CKD）风险。非奈利酮是一种强效且选择性的非甾体类盐皮质激素受体拮抗剂，以及钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i），可以降低 CKD 和 T2D 患者的肾脏和心血管风险。本文概述了一项研究的设计，旨在探讨非奈利酮与 SGLT2i 的联合治疗是否优于单一药物治疗。
CONFIDENCE（NCT05254002）是一项随机、对照、双盲、双模拟、国际、多中心、三臂、平行组、7.5 至 8.5 个月、2 期研究，纳入 807 例患有 T2D、2-3 期 CKD 和尿白蛋白/肌酐比值（UACR）≥300-<5000mg/g 的成年人。主要目的是证明 6 个月的非奈利酮联合 SGLT2i 恩格列净双重治疗在降低蛋白尿方面优于单一药物治疗。干预措施为每日一次非奈利酮 10mg 或 20mg（目标剂量）加恩格列净 10mg，或恩格列净 10mg 单药治疗，或非奈利酮 10mg 或 20mg（目标剂量）单药治疗。
主要结局是三组之间 UACR 自基线的相对变化。次要结局将进一步描述疗效和安全性，包括估计肾小球滤过率的变化和高钾血症的发生。
CONFIDENCE 正在评估非奈利酮与 SGLT2i 联合用于 CKD 和 T2D 成人的安全性、耐受性和疗效。如果显示出相加效应，早期和有效的双重非奈利酮和 SGLT2i 治疗可能会减缓疾病进展，并为 CKD 和 T2D 患者带来长期获益。
