Supplementary Material for: Inhibition of Calcium Release-Activated Calcium (CRAC) channels to Treat Acute Kidney Injury: Design and Rationale of the KOURAGE study

Introduction: Patients with severe acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF) experience poorer outcomes, including higher rates of in-hospital mortality, relative to patients with less severe AKI, or those without associated AHRF. Zegocractin is a calcium release-activated calcium (CRAC) channel inhibitor with potent anti-inflammatory and pulmonary endothelial protective properties. Preclinical and early phase clinical studies suggest that zegocractin may be an effective agent for the treatment of AKI. Methods: KOURAGE (NCT06374797) is a multicenter, phase 2, randomized, double blind, placebo-controlled trial that aims to enroll approximately 150 patients with severe AKI and AHRF. Eligible patients will be randomized 1:1 to receive a total of five daily doses of zegocractin intravenous emulsion (Auxora™) or matching placebo. The objective is to evaluate the safety and efficacy of Auxora in patients with severe AKI, with the primary efficacy endpoint defined as the number of days alive, ventilator-free and kidney replacement therapy (KRT)-free from the start of the first infusion of the study drug through Day 30. A key secondary efficacy endpoint is the proportion of patients with major adverse kidney events at Day 90. Conclusion: The KOURAGE trial will investigate the safety and efficacy of Auxora in patients with severe AKI and AHRF.

引言：合并急性低氧性呼吸衰竭（acute hypoxemic respiratory failure, AHRF）的重症急性肾损伤（acute kidney injury, AKI）患者，相较于轻症AKI患者或未合并AHRF的患者，预后更差，住院死亡率更高。泽考瑞坦（zegocractin）是一种钙释放激活钙（calcium release-activated calcium, CRAC）通道抑制剂，具备强效抗炎与肺内皮保护作用。临床前及早期临床研究显示，泽考瑞坦或可成为治疗AKI的有效药物。方法：KOURAGE（临床试验编号NCT06374797）是一项多中心、II期随机双盲安慰剂对照临床试验，计划纳入约150例重症AKI合并AHRF患者。符合入组条件的患者将按1:1比例随机分组，接受共计5个每日剂量的泽考瑞坦静脉乳剂（Auxora™）或匹配安慰剂。本试验旨在评估Auxora™在重症AKI患者中的安全性与有效性，主要有效性终点为自首次研究药物输注开始至第30天的存活天数、未行机械通气天数及未接受肾脏替代治疗（kidney replacement therapy, KRT）天数。关键次要有效性终点为第90天时发生主要不良肾脏事件的患者比例。结论：KOURAGE试验将评估Auxora™在重症AKI合并AHRF患者中的安全性与有效性。