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

基本信息

批准号：
10022510
负责人：
Phillip Chan
金额：
$ 99.19万
依托单位：
CYTOSORBENTS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-20 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10022510
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

项目摘要

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.

然而，浓缩红细胞（pRBC）输注可以挽救数十万非溶血性患者的生命。全世界每年都会发生输血反应，从轻微发烧和瘙痒到严重的生命危险威胁性反应，例如严重高钾血症、过敏反应和输血相关的急性肺损伤 (TRALI)。轻中度反应会导致患者不适、记录和测试成本增加。严重反应可能导致昂贵的重症监护、患者受伤甚至死亡，驾驶增加目前，没有简单的解决方案来净化造成的污染物。因此，CytoSorbents 正在开发 HemoDefend-RBC™，这是一种易于使用的、在线过滤器，可去除细胞外钾 (K+) 以及多种其他物质可能对输血受者造成潜在伤害的 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要么是残留成分。供血者的血液，或在血液储存过程中由于红细胞变质和溶血而产生的。对于需要大量输血的患者来说，过量 K+ 导致的高钾血症尤其危险。由于外伤和高风险手术、肾功能不全者以及儿科患者而导致的 pRBC 单位在美国，目前解决这些污染物的唯一方法是清洗设备。然而，这需要大量的时间、后勤和费用。通过重力流过滤 pRBC，无需额外的设备或能源。与当前的输血实践兼容，包括任何标准抗凝剂和添加剂该耐储存装置由惰性材料制成，不含易腐烂或可浸出的生物物质。组件，并且可以轻松进行伽马射线灭菌。 HemoDefend-RBC 过滤器利用并扩展了 CytoSorbents 专有的吸附性多孔聚合物用于医疗过滤的微珠技术平台是我们美国监管策略的最初重点。 HemoDefend-RBC 将获得批准用于从 pRBC 中去除细胞外 K+ 的输血点过滤器单位以降低输血相关高钾血症的风险可以达到极高。由于细胞表面离子泵失调和溶血，冷藏期间含量较高导致 K+ 从红细胞中释放出来拟议的 IIB 期过渡计划提供了资金，来自公司的配套资金，用于额外的研究、临床开发和制造扩大活动规模，推动美国和欧盟的监管批准和国际商业化 HemoDefend-RBC 过滤器的推出将提供一种易于使用、低成本的产品。安全有效地“清洗血液”中多种污染物的解决方案，无需花费任何费用，物流，以及目前物理清洗血液所需的时间。