Department of Anesthesia, St. Michael's Hospital, Toronto, Ontario, Canada.
Department of Anesthesiology and Pain Medicine, Physiology and Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
BMJ Open. 2023 Apr 6;13(4):e068363. doi: 10.1136/bmjopen-2022-068363.
Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies.
This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites.
The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.
NCT05126303.
急性肾损伤（AKI）是心脏手术后（CS）的常见并发症，与短期和长期不良预后相关。α-1-微球蛋白（A1M）是一种循环糖蛋白，具有抗氧化、血红素结合和线粒体保护机制。RMC-035 是 A1M 的一种改良、更具可溶性的变体，被提议作为一种新型靶向治疗蛋白，以预防 CS 相关 AKI（CS-AKI）。在四项临床 1 期研究中评估 RMC-035 时，发现其安全且一般耐受性良好。
这是一项 2 期、随机、双盲、自适应设计、平行组临床试验，评估 RMC-035 与安慰剂在大约 268 名高风险 CS-AKI 的心脏手术患者中的疗效。RMC-035 作为静脉输注给药。总共有 5 个剂量。给药基于术前估计的肾小球滤过率（eGFR），剂量为 1.3 或 0.65mg/kg。主要研究目标是评估 RMC-035 是否降低术后 AKI 的发生率，关键次要目标是评估 RMC-035 是否比安慰剂改善术后肾功能。一旦 134 名随机受试者完成给药，计划进行一次盲法中期分析，可能进行样本量重新评估。独立的数据监测委员会将在整个试验期间的预定间隔评估安全性和疗效数据。该研究是一项在大约 30 个地点进行的全球多中心研究。
该试验得到了威斯特法伦-利珀医师协会联合伦理委员会和明斯特大学（代码'2021-778f-A'）的批准，随后得到了参与地点的负责伦理委员会/相关机构审查委员会的批准。该研究符合良好临床实践、赫尔辛基宣言和其他适用法规。本研究结果将发表在同行评议的科学期刊上。
NCT05126303。
