Brixner Veronika, Kiessling Arndt-Holger, Madlener Katharina, Müller Markus M, Leibacher Johannes, Dombos Sarah, Weber Iuliia, Pfeiffer Hans-Ulrich, Geisen Christof, Schmidt Michael, Henschler Reinhard, North Anne, Huang Norman, Mufti Nina, Erickson Anna, Ernst Christine, Rico Salvador, Benjamin Richard J, Corash Laurence M, Seifried Erhard
Institute for Transfusion Medicine and Immunohematology of Johann Wolfgang Goethe University and German Red Cross Blood Donor Service, Frankfurt am Main, Germany.
Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
Transfusion. 2018 Apr;58(4):905-916. doi: 10.1111/trf.14528. Epub 2018 Mar 1.
Nucleic acid-targeted pathogen inactivation technology using amustaline (S-303) and glutathione (GSH) was developed to reduce the risk of transfusion-transmitted infectious disease and transfusion-associated graft-versus-host disease with red blood cell (RBC) transfusion.
A randomized, double-blind, controlled study was performed to assess the in vitro characteristics of amustaline-treated RBCs (test) compared with conventional (control) RBCs and to evaluate safety and efficacy of transfusion during and after cardiac surgery. The primary device efficacy endpoint was the postproduction hemoglobin (Hb) content of RBCs. Exploratory clinical outcomes included renal and hepatic failure, the 6-minute walk test (a surrogate for cardiopulmonary function), adverse events (AEs), and the immune response to amustaline-treated RBCs.
A total of 774 RBC unis were produced. Mean treatment difference in Hb content was -2.27 g/unit (95% confidence interval, -2.61 to -1.92 g/unit), within the prespecified equivalence margins (±5 g/unit) to declare noninferiority. Amustaline-treated RBCs met European guidelines for Hb content, hematocrit, and hemolysis. Fifty-one (25 test and 26 control) patients received study RBCs. There were no significant differences in RBC usage or other clinical outcomes. Observed AEs were within the spectrum expected for patients of similar age undergoing cardiovascular surgery requiring RBCs transfusion. No patients exhibited an immune response specific to amustaline-treated RBCs.
Amustaline-treated RBCs demonstrated equivalence to control RBCs for Hb content, have appropriate characteristics for transfusion, and were well tolerated when transfused in support of acute anemia. Renal impairment was characterized as a potential efficacy endpoint for pivotal studies of RBC transfusion in cardiac surgery.
开发了使用氨甲环酸（S - 303）和谷胱甘肽（GSH）的核酸靶向病原体灭活技术，以降低红细胞（RBC）输血导致的输血传播感染性疾病和输血相关移植物抗宿主病的风险。
进行了一项随机、双盲、对照研究，以评估氨甲环酸处理的红细胞（试验组）与传统红细胞（对照组）的体外特性，并评估心脏手术期间及术后输血的安全性和有效性。主要设备疗效终点是红细胞生产后的血红蛋白（Hb）含量。探索性临床结果包括肾衰竭和肝功能衰竭、6分钟步行试验（心肺功能的替代指标）、不良事件（AE）以及对氨甲环酸处理的红细胞的免疫反应。
共生产了774个红细胞单位。Hb含量的平均治疗差异为-2.27 g/单位（95%置信区间，-2.61至-1.92 g/单位），在预先设定的等效界限（±5 g/单位）内，表明非劣效性。氨甲环酸处理的红细胞符合欧洲关于Hb含量、血细胞比容和溶血的指南。51名患者（25名试验组和26名对照组）接受了研究红细胞输血。红细胞使用量或其他临床结果无显著差异。观察到的不良事件在接受需要红细胞输血的心血管手术的相似年龄患者预期范围内。没有患者表现出对氨甲环酸处理的红细胞的特异性免疫反应。
氨甲环酸处理的红细胞在Hb含量方面与对照红细胞等效，具有适合输血的特性，在用于支持急性贫血输血时耐受性良好。肾功能损害被确定为心脏手术中红细胞输血关键研究的潜在疗效终点。
