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

抽象的。选择性细胞增殖装置（SCD）是一种可能挽救生命的治疗COVID-19诱导的 呼吸功能不全（RI）和急性呼吸窘迫综合征（ARDS），这是COVID-19的主要原因 死亡SCD是一种免疫调节器械，用于由中心静脉导管给药的体外血液回路中。 静脉导管和连续性肾脏替代治疗（CRRT）泵系统，之前已 临床上用于治疗急性肾损伤（阿基），并已证明对白细胞（LE）和细胞毒性有影响。 减少炎症的因子。有证据表明，高浓度细胞因子的过度炎症 并且LE升高在COVID-19中的ARDS的发展中起关键作用。COVID-19发展成为一个穆尔- 大叶性病毒性肺炎，通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），如果严重，则为ARDS。ICU COVID-19患者的死亡率，沿着ARDS MV接近50%，对于需要CRRT的并发阿基的类似患者，已发表的死亡率 接近70%。报告表明疾病进展时间过程为呼吸困难前8天和呼吸困难后10天。 急性呼吸窘迫综合征，展示了一个潜在的治疗干预的重要时间表。 使用经外周静脉置入中心静脉导管（PICC）进行SCD治疗， cular access和Aquadex SmartFlow（ASF）系统治疗ICU外的RI，以防止进展为 ARDS。 长期目标：收集提交FDA IDE补充申请所需的临床前数据 SCD通过PICC血管通路（SCD-PICC），以便在进展之前治疗与COVID-19相关的RI- 需要机械通气的ARDS。SCD-PICC治疗将使用ASF泵系统开发， 沿着使用SCD的修订后局部柠檬酸盐抗凝（RCA）方案， 白细胞免疫调节装置以及血液过滤器，其中SCD的中空纤维的外部， 纤维是血细胞接触表面，SCD的中空纤维用于产生超滤液（UF）。 目标1。使用来自当地屠宰场的新鲜血液进行体外血液回路（IVBC）研究，以评估使用 将SCD作为免疫调节器械和血液滤过器，确认回路伊卡和柠檬酸盐充足 的拔除.目标二。作为FDA要求的一部分，将评价SCD-PICC回路组件的血液相容性 生物相容性和安全性测试，以确认功能正常，无溶血或血栓形成。目标3。试点 建立猪特异性呼吸道冠状病毒（PRCV）引起的ALI猪模型的研究， 适用于SCD-PICC治疗的评估。预期健康相关影响：COVID-19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.