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.

输注红细胞(PRBC)可以挽救生命。然而，数十万的非溶血性 全世界每年都会发生输血反应，从轻微的发烧和瘙痒，到严重的生命- 严重高钾血症、过敏反应和输血相关的急性肺损伤等威胁反应 (TRALI)。轻度-中度反应会导致患者不适、记录和测试成本，而 严重的反应会导致昂贵的重症监护，病人受伤，甚至死亡，驾驶增加 医疗保健利用率和成本。目前，没有简单的解决方案来净化导致 这些反应来自pRBC。因此，CytoSorbents正在开发HemoDefend-红细胞™，一种易于使用的， 在线过滤器，用于去除胞外钾(K+)以及从 可能对受血者造成潜在伤害的红细胞，包括游离血红蛋白、生物活性脂质、 细胞因子、反应酶和抗体。这些污染物要么是来自 献血，或在血液储存过程中因红细胞变性和溶血而产生。 过量K+引起的高钾血症在需要大量输血的患者中尤其危险 因创伤和高危手术、肾功能不全者以及儿科 病人。在美国，目前解决这些污染物的唯一方法是清洗设备 鲜血。然而，这需要相当长的时间、物流和费用。HemoDefend-RBC旨在 通过重力流过滤pRBC，不需要额外的设备或能源。过滤是 符合目前的输血做法，包括任何标准的抗凝剂和添加剂 解决办法。货架稳定装置是由惰性材料制成的，没有易腐烂或可浸出的生物 并且可以很容易地伽马灭菌。 HemoDefend-RBC过滤器利用并扩展了CytoSorbents专有的吸附多孔聚合物 医疗过滤的微珠技术平台。我们美国监管战略的最初重点是 血液防御-RBC将批准输液点过滤器从pRBC中去除细胞外K+ 以降低输血相关高钾血症的风险。钾可以达到极高的 冷藏期间由于细胞表面离子泵失调和溶血而导致的高水平 导致K+从红细胞中释放出来。拟议的第二期B期桥梁方案提供资金， 来自该公司的配套资金，用于额外的研究、临床开发和制造 扩大活动，以推动美国和欧盟的监管批准和国际商业化 HemoDefend-RBC。HemoDefend-RBC过滤器的上市将提供易于使用、成本低的 一种安全有效的解决方案，可以安全、有效地“洗血”各种污染物，而且不需要花费任何费用。 后勤，以及目前物理清洗血液所需的时间。