X-COR Therapeutics is creating the first extracorporeal CO2 removal (ECCO2R) device that usesdialysis-like approaches to accessibly treat hypercapnic respiratory failure (HRF) patients. HRF is adevastating consequence of critical lung disease caused by chronic obstructive pulmonary disease (COPD)and other respiratory disorders including acute respiratory distress syndrome (ARDS), a common complicationof COVID-19. The current standard of care for severe disease is invasive mechanical ventilation, which resultsin a ~30% mortality rate and increased susceptibility to ARDS. While use of protective ventilatory strategiesreduces mortality, resultant hypercapnia from protective ventilation resembles diseases like COPD. In bothcases, impaired ventilation causes increased carbon dioxide (CO2) levels that lead to acidosis, coma, anddeath. For patients with hypercapnia, extracorporeal technologies that deliver oxygen and remove gaseousCO2 (e.g. ECMO) present possible alternatives but are highly invasive and costly. They require high blood flowrates (>1 L/min) and large-bore cannula only deployable in specialized facilities.Here, we propose investigating a hybrid device that resembles a hemodialysis-like blood filtration cartridge thatcontains a novel configuration of two filtration fibers for bicarbonate dialysis and gaseous CO2 capture. Highefficiency CO2 removal allows a low blood rate of <250 ml/min, thus allowing small catheters (<13.5 Fr) toreplace the 28-30 Fr cannula used today in most extracorporeal therapies. Less invasive and standardvascular access makes this therapy accessible and enables its use in parallel with invasive mechanicalventilation. With parallel therapy, the proposed device can prevent hypercapnia that results from protectiveventilation and enable safer use of invasive mechanical ventilation with earlier extubation. Because it can useexisting hemodialysis systems, the device can be deployed with existing workflows and capital equipment.The objective of this Phase I SBIR project is to optimize and then investigate ventilatory benefits from using ahybrid membrane filtration device that removes CO2 from ultra-low extracorporeal blood flow. Aim 1 is todetermine optimal device geometries and operating parameters (e.g. size, fiber pack density, and fiber ratio)that meet desired CO2 capture requirements through iterative modification of a novel design using scalableproduction methods. Each iteration will be evaluated using bench-top ex-vivo perfusion testing. Aim 2 is toinvestigate the impact that extracorporeal CO2 capture has on patient spontaneous and assisted ventilatoryrequirements using a series of physiologic computational models using patient-specific boundary conditions.Successful completion of this project will result in a manufacture-ready device with candidate geometries andoperating parameters for pre-clinical testing. This device will be able to: 1) remove >30% of CO2 produced; 2)be produced using scalable manufacturing; and 3) be interoperable with existing hemodialysis platforms. Thisis a critical step for advancing toward future pre-clinical and clinical studies in support of FDA approval.
Public Health Relevance Statement: PROJECT RELEVANCE
The proposed device and methodology meet a critical unmet need for a safer, more accessible treatment that
removes carbon dioxide from the blood of patients with hypercapnic respiratory failure (HRF) resulting from
chronic obstructive pulmonary disease (COPD) or complications during treatment of severe COVID-19. Current
treatment methods rely on invasive mechanical ventilation that require resource-heavy intensive care unit
hospitalizations and can potentially further damage the lungs. This proposal investigates a novel approach for
carbon dioxide removal in a system that is comparable to hemodialysis instead of more invasive systems like
ECMO, allowing use of safer ventilatory protocols and shortening intensive care unit stays.
Project Terms: Acidosis ; Adoption ; Affect ; Bicarbonates ; HCO3 ; Hydrogen Carbonates ; Blood ; Blood Reticuloendothelial System ; Blood Vessels ; vascular ; Capital ; Carbon Dioxide ; CO2 ; Carbonic Anhydride ; Chronic Disease ; Chronic Illness ; chronic disorder ; Clinical Protocols ; Clinical Research ; Clinical Study ; Coma ; Comatose ; Complication ; Cessation of life ; Death ; Dialysis procedure ; Dialysis ; dialysis therapy ; Disease ; Disorder ; Equilibrium ; balance ; balance function ; Equipment ; Extracorporeal Membrane Oxygenation ; Filtration ; Filtration Fractionation ; Future ; Goals ; Hemodialysis ; Hemodialyses ; Hospitalization ; Hospital Admission ; Hybrids ; Hypercapnia ; carbon dioxide retention ; elevated carbon dioxide ; hypercarbia ; increased level Carbon dioxide ; Inflammation ; Intensive Care Units ; Ions ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Lung ; Lung Respiratory System ; pulmonary ; Lung Compliance ; Lung diseases ; Pulmonary Diseases ; 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coronavirus disease/ARDS ; coronavirus disease/acute respiratory distress syndrome ; severe acute respiratory syndrome coronavirus 2 associated ARDS ; severe acute respiratory syndrome coronavirus 2 associated acute respiratory distress syndrome ; severe acute respiratory syndrome coronavirus 2 induced ARDS ; severe acute respiratory syndrome coronavirus 2 induced acute respiratory distress syndrome ; severe acute respiratory syndrome coronavirus 2 related ARDS ; severe acute respiratory syndrome coronavirus 2 related acute respiratory distress syndrome ; severe acute respiratory syndrome coronavirus 2/ARDS ; severe acute respiratory syndrome coronavirus 2/acute respiratory distress syndrome ; COVID-19 patient ; COVID infected patient ; COVID patient ; COVID positive patient ; COVID-19 infected patient ; COVID-19 positive patient ; COVID19 patient ; COVID19 positive patient ; SARS-CoV-2 infected patient ; SARS-CoV-2 patient ; SARS-CoV-2 positive patient ; coronavirus disease 2019 infected patient ; 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