SCD-PICC Therapy for Respiratory Insufficiency associated with COVID-19 in non-ICU settings

抽象的。选择性细胞遗传学装置(SCD)是新冠肺炎诱导的一种潜在的挽救生命的治疗方法 新冠肺炎的诱因之一--呼吸功能不全和急性呼吸窘迫综合征 死亡。SCD是一种免疫调节设备，用于体外循环血液，由中央 静脉导管和连续性肾脏替代治疗(CRRT)泵系统，以前 临床上用于治疗急性肾损伤(AKI)，并已证明对白细胞(LE)和细胞因子的影响 减少炎症的运动。有证据表明，高度炎症和高浓度的细胞因子 LE升高在新冠肺炎急性呼吸窘迫综合征的发生发展中起关键作用。新冠肺炎的发展是一种多层次的 小叶病毒性肺炎，常进展为需要机械通气的呼吸功能不全(RI) (MV)、急性肺损伤(ALI)和ARDS(如果情况严重)。重症监护病房新冠肺炎患者合并急性呼吸窘迫综合征患者的死亡率 MV接近50%，对于并发AKI需要CRRT的相似患者，公布的死亡率 接近70%。报告显示，病情进展的时间为呼吸困难前8天和10天至 ARDS，为潜在的治疗干预展示了一个重要的时间框架。这项提案计划去... 开发一种形式的SCD治疗，可以利用外周插入中心静脉导管(PICC)血管- Circle Access和Aquadex SmartFlow(ASF)系统用于治疗ICU外的RI，以防止进展到 阿兹。 长期目标：收集提交FDA IDE补充剂使用所需的临床前数据 经PICC血管通路SCD治疗新冠肺炎相关RI 西昂呼叫ARDS，需要机械通风。SCD-PICC疗法将使用ASF泵系统开发- 低流速下的TEM，以及使用SCD AS的修订的区域柠檬酸盐抗凝(RCA)方案 既有白细胞免疫调节装置，也有血液过滤器，其中SCD中空纤维的外部- BERS是与血细胞接触的表面，SCD的中空纤维用于产生超滤液(UF)。 目的1.使用当地屠宰场的新鲜血液进行体外血液循环(IVBC)研究，以评估利用... ING SCD既是一种免疫调节装置，也是一种血液过滤器，确定了适当的ICA和柠檬酸盐电路 移走。目标2.作为FDA要求的一部分，将评估SCD-PICC电路组件的血液兼容性 生物兼容性和安全性测试，以确认功能正常，没有溶血或血栓形成。目标3.试点 猪呼吸道冠状病毒致急性肺损伤动物模型的建立 适用于SCD-PICC治疗的评估。预期的健康相关影响：新冠肺炎的减少 从RI进展为ARDS，需要机械通气的患者较少。

Abstract. The Selective Cytopheretic Device (SCD) is a potentially lifesaving treatment for COVID-19 induced respiratory insufficiency (RI) and Acute Respiratory Distress Syndrome (ARDS), a driving cause of COVID-19 deaths. SCD is an immunomodulatory device used in an extracorporeal blood circuit administered by a central venous catheter and continuous renal replacement therapy (CRRT) pump system, which has been previously clinically used to treat acute kidney injury (AKI) and has demonstrated an impact on leukocytes (LE) and cyto- kines reducing inflammation. Evidence suggests that hyperinflammation with high concentrations of cytokines and elevated LE plays a critical role in the development of ARDS in COVID-19. COVID-19 develops as a mul- tilobar viral pneumonitis and often progresses to respiratory insufficiency (RI) requiring mechanical ventilation (MV), acute lung injury (ALI) and, if severe, ARDS. Mortality for ICU patients with COVID-19, along with ARDS on MV approaches 50% and for similar patients with concurrent AKI requiring CRRT published mortality rates approach 70%. Reports suggest a disease progression time course with 8 days before dyspnea and 10 days to ARDS, demonstrating a significant timeframe for potential treatment intervention.This proposal plans to de- velop a form SCD therapy that can be administered utilizing peripherally inserted central catheter (PICC) vas- cular access and Aquadex SmartFlow (ASF) system to treat RI outside the ICU, to prevent progression to ARDS. Long term objective: To gather preclinical data required for the submission of an FDA IDE supplement to use the SCD via PICC vascular access (SCD-PICC) in order to treat RI associated with COVID-19 prior to progres- sion to ARDS requiring mechanical ventilation. SCD-PICC therapy will be developed using the ASF pump sys- tem at a low flow rate, along with a revised regional citrate anticoagulation (RCA) protocol utilizing SCD as both a leukocyte immunomodulatory device as well as a hemofilter, where the outside of the SCD’s hollow fi- bers are the blood cell-contacting surfaces and SCD’s hollow fibers are used to generate ultrafiltrate (UF). Aim 1. In vitro blood circuit (IVBC) studies using fresh blood from a local abattoir to assess feasibility of utiliz- ing SCD as both an immunomodulatory device and a hemofilter, confirming adequate circuit iCa and citrate removal. Aim 2. Hemocompatibility will be evaluated for SCD-PICC circuit components as part of FDA required biocompatibility and safety testing to confirm proper function without hemolysis or thrombosis. Aim 3. Pilot studies to establish a porcine model of ALI caused by porcine specific respiratory corona virus (PRCV) to be adapted for assessment of SCD-PICC therapy. Anticipated Health Related Impact: a reduction of COVID-19 progression from RI to ARDS with fewer patients requiring mechanical ventilation.