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

SCD-PICC 治疗非 ICU 中与 COVID-19 相关的呼吸功能不全

基本信息

批准号：
10481579
负责人：
Christopher Pino
金额：
$ 32.53万
依托单位：
INNOVATIVE BIOTHERAPIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2023-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10481579
关键词：
Abattoirs Acute Lung Injury Acute Renal Failure with Renal Papillary Necrosis Acute Respiratory Distress Syndrome Adrenal Cortex Hormones Adult Age Anticoagulation Automobile Driving Biological Markers Biological Response Modifier Therapy Blood Blood Cells Blood Vessels Blood flow CCL2 gene COVID-19 COVID-19 intervention COVID-19 mortality COVID-19 patient COVID-19 treatment COVID-19/ARDS Calcium ion Catheters Cell Separation Childhood Citrates Clinical Clinical Trials Coronavirus Data Development Devices Dialysis procedure Disease Disease Progression Dyspnea Early Intervention Early treatment Emergency Situation End stage renal failure Enrollment Environment Excision Extracorporeal Membrane Oxygenation Family suidae Ferritin Fiber Health Hemolysis IL6 gene ITGAM gene In Vitro Inflammation Inflammatory Intensive Care Units Interleukin-1 Receptors Interleukin-10 Interleukin-6 Intervention Intubation Leukocytes Lung Masks Mechanical ventilation Multi-Institutional Clinical Trial Nurses Patients Peripheral Pilot Projects Plasma Play Process Protocols documentation Publishing Pulmonary Inflammation Pump Renal Replacement Therapy Reporting Respiratory Insufficiency Respiratory Therapy Risk Role Sepsis Serious Adverse Event Serum Signal Transduction Subgroup Surface Survivors System Systemic Inflammatory Response Syndrome Technology Testing Thrombosis Time Toxic effect Venous Viral Viral Pneumonia Work biomaterial compatibility clinical translation cytokine hemocompatibility immunomodulatory therapies immunoregulation improved innovation mortality neutrophil porcine model pre-clinical prevent remdesivir respiratory safety and feasibility safety testing solute ventilation

项目摘要

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.

摘要：选择性细胞分离装置 (SCD) 是治疗 COVID-19 的一种潜在救命方法。呼吸功能不全 (RI) 和急性呼吸窘迫综合征 (ARDS)，这是 COVID-19 的一个驱动因素 SCD 是一种由中央管理的体外血液回路中使用的免疫调节装置。静脉导管和连续肾脏替代治疗 (CRRT) 泵系统，该系统之前已临床上用于治疗急性肾损伤 (AKI)，并已证明对白细胞 (LE) 和细胞因子有影响有证据表明，高浓度的细胞因子可减轻炎症。在 COVID-19 中，LE 升高在 ARDS 的发展中发挥着关键作用。蒂洛巴病毒性肺炎，常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) 以及重症监护室 (ICU) COVID-19 患者的死亡率以及 ARDS。 MV 接近 50%，并且对于同时患有 AKI 且需要 CRRT 的类似患者，公布的死亡率接近 70% 的报告显示，疾病进展时间为呼吸困难前 8 天，呼吸困难后 10 天。 ARDS，展示了潜在治疗干预的重要时间框架。该提案计划取消 velop 插入了一种 SCD 疗法，可以利用外周中心静脉导管 (PICC) 进行给药血管通路和 Aquadex SmartFlow (ASF) 系统可在 ICU 外治疗 RI，以防止进展为 ARDS。长期目标：收集提交 FDA IDE 补充剂使用所需的临床前数据通过 PICC 血管通路 (SCD-PICC) 进行 SCD，以便在病情进展之前治疗与 COVID-19 相关的 RI 将使用 ASF 泵系统开发针对需要机械通气的 ARDS 的治疗方案。 TEM 以低流速，以及使用 SCD 作为修订的区域柠檬酸盐抗凝 (RCA) 方案既是白细胞免疫调节装置又是滤血器，其中 SCD 的中空纤维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循环 (IVBC) 研究，以评估利用将 SCD 作为免疫调节装置和血滤器，确认足够的 iCa 和柠檬酸盐回路目标 2。作为 FDA 要求的一部分，将评估 SCD-PICC 电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。建立由猪特异性呼吸道冠状病毒（PRCV）引起的 ALI 猪模型的研究适合评估 SCD-PICC 治疗的预期健康相关影响：COVID-19 的减少。从 RI 进展为 ARDS，需要机械通气的患者较少。