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

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.