Ostermann Marlies, Corteville David C, Doi Kent, Koyner Jay L, Lamy Andre, Li Gerry, Solinsky Christine M, Winterberg Pamela D, Smith William T, Mehta Ravindra L, Murray Patrick T, Shaw Andrew D, Zarbock Alexander, Engelman Daniel T
Critical Care and Nephrology, NHS Foundation Trust, Guy's and St Thomas, London, UK.
Department of Cardiology, Rochester Regional Health, Rochester, USA.
Trials. 2025 May 30;26(1):181. doi: 10.1186/s13063-025-08895-7.
Cardiac procedures, particularly those requiring cardiopulmonary bypass (CPB), are associated with the development of cardiac surgery-associated acute kidney injury (CSA-AKI). Development of CSA-AKI occurs as a result of inflammation, uncontrolled complement activation, and kidney cell damage. In patients with preoperative renal impairment, such as those with chronic kidney disease (CKD), there is an increased risk of both CSA-AKI and poorer clinical outcomes. Currently, there are limited effective, targeted pharmacological interventions for the prevention or treatment of CSA-AKI, although emerging therapies are being investigated, particularly in patients with existing CKD. The ARTEMIS (RAvulizumab to PRotect PaTients with Chronic Kidney DisEase froM CSA-AKI and Subsequent Major Adverse Kidney Events) trial will assess the efficacy and safety of ravulizumab (a complement C5 inhibitor) in reducing the risk of major adverse kidney events (MAKE) in patients with preoperative CKD undergoing non-emergent cardiac surgery with CPB.
This trial is currently recruiting patients with CKD who have planned cardiac surgery requiring CPB including coronary artery bypass grafting, valve replacement or repair, or combined procedures. This is a phase 3, randomized, double-blind, placebo-controlled, global study assessing the efficacy and safety of a single preoperative dose of ravulizumab. These outcomes will be assessed using the occurrence of MAKE and its components, as well as the occurrence and severity of CSA-AKI throughout the study period.
Complement activation is known to occur during and after cardiac procedures as a result of CPB and ischemia-reperfusion injury, leading to a cycle of cell damage and death. Therefore, it is hypothesized that preoperative administration of ravulizumab will provide immediate and complete complement inhibition, which will be sustained throughout the surgical period, preventing the uncontrolled complement activation associated with the development of CSA-AKI, thus minimizing poor outcomes for patients.
ClinicalTrials.gov NCT05746559. Registered on February 27, 2023.
心脏手术，尤其是那些需要体外循环（CPB）的手术，与心脏手术相关的急性肾损伤（CSA-AKI）的发生有关。CSA-AKI的发生是炎症、补体激活失控和肾细胞损伤的结果。在术前肾功能受损的患者中，如慢性肾脏病（CKD）患者，发生CSA-AKI的风险增加，临床结局也较差。目前，对于CSA-AKI的预防或治疗，有效的靶向药物干预措施有限，不过正在研究新出现的疗法，特别是在已有CKD的患者中。ARTEMIS（用ravulizumab保护慢性肾脏病患者免受CSA-AKI及随后的主要不良肾脏事件影响）试验将评估ravulizumab（一种补体C5抑制剂）在降低接受非急诊CPB心脏手术的术前CKD患者发生主要不良肾脏事件（MAKE）风险方面的疗效和安全性。
本试验目前正在招募计划进行需要CPB的心脏手术的CKD患者，包括冠状动脉搭桥术、瓣膜置换或修复术或联合手术。这是一项3期、随机、双盲、安慰剂对照的全球研究，评估术前单次剂量ravulizumab的疗效和安全性。这些结局将通过整个研究期间MAKE及其组成部分的发生情况，以及CSA-AKI的发生情况和严重程度来评估。
已知在心脏手术期间和术后，由于CPB和缺血再灌注损伤会发生补体激活，导致细胞损伤和死亡的循环。因此，推测术前给予ravulizumab将提供即时和完全的补体抑制作用，这种作用将在整个手术期间持续，防止与CSA-AKI发生相关的补体激活失控，从而将患者的不良结局降至最低。
ClinicalTrials.gov NCT05746559。于2023年2月27日注册。
