pRBC Contaminant Removal with Hemocompatible Porous Polymer Beads

使用血液相容性多孔聚合物珠去除 pRBC 污染物

• 批准号: 9765390
• 负责人: Phillip Chan
• 金额: $ 98.31万
• 依托单位: CYTOSORBENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-20 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765390
• 关键词: Acute Lung Injury; Address; Advanced Development; Adverse event; Aging; Aluminum; Anaphylaxis; Antibodies; Anticoagulants; Autologous; Automobile Driving; Biological; Blood; Blood donor; Cell surface; Cellular Morphology; Cellular Structures; Cessation of life; Chemistry; Clinical; Clinical Research; Critical Care; Cross-Over Studies; Cryopreservation; Custom; Data; Deterioration; Development; Device Designs; Devices; Documentation; Endothelium; Energy-Generating Resources; Ensure; Enzyme Reactivation; Equipment; Erythrocyte Transfusion; Erythrocytes; Evaluation; Excision; Fever; Filtration; Force of Gravity; Funding; Glucose; Health Care Costs; Hemoglobin; Hemolysis; Hour; Housing; Howard Temin Award; In Vitro; Inflammatory; Informed Consent; Injections; Injury; Institutional Review Boards; Instruction; Intensive Care; International; Investigation; Ion Pumps; Kidney Failure; Label; Laboratories; Leukocytes; Life; Lipids; Logistics; Mediating; Medical; Molds; Outcome; Packed Red Blood Cell Transfusion; Particulate; Patients; Performance; Permeability; Phase; Polymers; Population; Potassium; Process; Production; Protocols documentation; Pruritus; Radiolabeled; Reaction; Recovery; Research; Residual state; Risk; Safety; Shipping; Side; Site; Specific qualifier value; Steel; Sterilization; Technology; Testing; Time; Transfusion; Trauma; Validation; Vascular blood supply; arm; blood product; bridge program; clinical development; commercialization; cost; cytokine; design; extracellular; health care service utilization; healthy volunteer; hemocompatibility; high risk; hyperkalemia; improved; lactate dehydrogenase 2; manufacturing scale-up; normal aging; novel; pediatric patients; prevent; product development; programs; research study; success; surgical risk; tool; usability; validation studies

Packed red blood cell (pRBC) transfusions save lives. However, hundreds of thousands of non-hemolytic transfusion reactions occur each year worldwide, ranging from mild fever and pruritis, to serious life- threatening reactions such as severe hyperkalemia, anaphylaxis, and transfusion-related acute lung injury (TRALI). Mild-moderate reactions drive patient discomfort, documentation, and testing costs while serious reactions can result in expensive intensive care, patient injury, and even death, driving increased healthcare utilization and cost. Currently, there is no easy solution to purify contaminants that cause these reactions from pRBCs. Therefore, CytoSorbents is developing HemoDefend-RBC™, an easy-to-use, in-line filter, that removes extracellular potassium (K+) plus a broad spectrum of other substances from pRBCs that may potentially harm transfusion recipients, including free hemoglobin, bioactive lipids, cytokines, reactive enzymes, and antibodies. These contaminants are either residual components from donor blood, or are generated during blood storage due to RBC deterioration and hemolysis. Hyperkalemia from excessive K+ is particularly a risk in patients requiring transfusion of large numbers of pRBC units due to trauma and high-risk surgery, those with renal insufficiency, as well as in pediatric patients. In the U.S., the only currently available means to address these contaminants is to wash units of blood. However, this takes considerable time, logistics and expense. HemoDefend-RBC is designed to filter pRBCs via gravity flow and requires no additional equipment or energy source. Filtration is compatible with current transfusion practices, including any of the standard anti-coagulants and additive solutions. The shelf-stable device is made of inert materials with no perishable or leachable biological components and can be readily gamma-sterilized. The HemoDefend-RBC filter leverages and extends CytoSorbents’ proprietary adsorptive porous polymer bead technology platform for medical filtration. The initial focus of our U.S. regulatory strategy for HemoDefend-RBC will be the approval of a point-of-transfusion filter to remove extracellular K+ from pRBC units in order to reduce the risk of transfusion-associated hyperkalemia. Potassium can reach extremely high levels during cold storage due to the dysregulation of cell surface ion pumps and hemolysis that causes K+ to be released from red cells. The proposed Phase IIB bridge program provides funding, with matching funds from the company, for additional research, clinical development, and manufacturing scale-up activities, to drive U.S. and E.U. regulatory approval and international commercialization of HemoDefend-RBC. Availability of the HemoDefend-RBC filter will provide an easy-to-use, low cost solution to safely and effectively “wash blood” of a broad range of contaminants without the expense, logistics, and time currently required to physically wash blood.

挤满了红细胞（PRBC）输血挽救生命。但是，成千上万的非溶聚 输血反应每年每年发生，从轻度发烧和瘙痒，到严重的生活 - 威胁性反应，例如严重的高钾血症，过敏反应和输血相关的急性肺损伤 （Trali）。轻度中度反应会导致患者不适，文档和测试成本，而 严重的反应会导致昂贵的重症监护，患者受伤甚至死亡，驾驶增加 医疗保健利用和成本。目前，没有简单的解决方案可以净化污染物 PRBC的这些反应。因此，Cytosorbents正在开发易于使用的HemodeFend-RBC™， 在线过滤器，它去除了细胞外钾（K+）以及其他广泛的物质 可能会损害输血接受者的PRBC，包括游离血红蛋白，生物活性脂质， 细胞因子，反应酶和抗体。这些污染物是来自 供体血液，或由于RBC定义和溶血而产生的血液中产生。 对于需要翻译大量的患者，来自多余K+的高钾血症尤其是一种风险 由于创伤和高风险手术，肾功能不全的PRBC单位以及小儿 患者。在美国，目前唯一可用的解决这些污染物的方法是清洗单元 血液。但是，这需要大量时间，物流和费用。 HemodeFend-RBC设计为 通过重力流过滤PRBC，不需要其他设备或能源。过滤是 与当前的输血实践兼容，包括任何标准的抗凝剂和添加剂 解决方案。货架稳定的设备由惰性材料制成，没有易腐或杠杆生物学 组件，并且可以容易化为伽马菌。 血管fend-rbc滤波器的利用并扩展细胞吸附剂的专有吸附性多孔聚合物 医疗过滤的珠技术平台。我们美国监管策略的最初重点 血管fend-rbc将获得转移点过滤器的批准，以从PRBC中删除细胞外K+ 单位以降低输血相关的高钾血症的风险。钾可以极端到达 由于细胞表面离子泵的失调和溶血引起的冷藏期间高水平 导致K+从红细胞释放。拟议的IIB桥计划提供资金，并 匹配公司的资金，以进行其他研究，临床开发和制造 扩大活动，以驱动美国和欧盟监管部门的批准和国际商业化 血管fend-rbc。血管fend-RBC过滤器的可用性将提供易于使用的低成本 解决方案，可安全有效地“清洗血液”，无需费用， 物流，目前需要进行物理洗血所需的时间。