ABSTRACT
SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: The SARS-CoV-2 virus preferentially attacks alveolar Type 2 cells that have the membrane ACE2 receptors. Type 2 cells are the surfactant producing cells in the lung. Damage to Type 2 cells can result in decreased/abnormal surfactant production leading to ARDS and respiratory failure. Surfactant is further inactivated by inflammatory proteins during ARDS. We sought to evaluate the feasibility, safety and tolerability of surfactant therapy in COVID-19 associated ARDS using a synthetic surfactant, lucinactant. METHODS: Open-label, single arm, multicenter study (NCT04389671) in adults with COVID-19 associated ARDS, who have been intubated and on mechanical ventilation (MV) with a P/F ratio <= 300. COVID-19 infection was confirmed by PCR. Lucinactant at a dose of 160 ml (∼80 mg TPL/kg lean body weight) was delivered intratracheally within 7 days of intubation. Retreatment was allowed at >= 6-hour intervals if subjects remained on MV. Assessments included time to deliver the dose, physiologic parameters of oxygenation (P/F, OI, PaO2), FiO2, PaCO2, lung compliance (CL) from baseline (pre-dosing) through day 5 post-dosing. Safety parameters included peri-dosing (PD) events (bradycardia, desaturation, hypotension, regurgitation) and adverse events through 30 days post dosing. RESULTS: 20 subjects were enrolled and 19 received at least one dose. Five subjects received 2 doses of lucinactant. The mean age of subjects was 49 years, 80% were male, 60% were white. The mean time to administer the dose was 31 minutes. FiO2 requirements, PaO2 and PCO2 remained stable throughout the 5-day period post dosing. Baseline mean P/F ratio and standard deviation (SD) was 196 (68), 179 (57) at 12 hours and 193 (61) at day 1 post-dosing, followed by a gradual increase to 223 (105) at day 5. Mean CL increased from 40.5 (16) at baseline to 49.8 (23) at day 5. Seven subjects (37%) died, 6 due to secondary infection and sepsis > 13 days after dosing. Two subjects experienced transient PD events (desaturation, regurgitation). Lucinactant administration in severe ARDS due to COVID-19 was safe and generally well tolerated. The incidence of PD events was low. Stable to improved physiologic parameters of oxygenation were observed post dosing. Increasing the dose and number of administrations may provide additional benefit. CLINICAL IMPLICATIONS: The data support continued study of lucinactant in ARDS patients. DISCLOSURES: Consultant relationship with Windtree Therapeutics Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Consultant relationship with Windtree Therapeutics Inc. Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Removed 03/31/2022 by Carlos Guardia Advisory Committee Member relationship with Windtree, inc Please note: 4/2021-2/2022 Added 04/04/2022 by Yuh-Chin Huang, value=Grant/Research No relevant relationships Added 04/04/2022 by Peter Morris, value=Consulting fee Removed 04/04/2022 by Peter Morris Employee relationship with Windtree Therapeutics, Inc. Please note: 2008-2022 Added 04/04/2022 by Phillip Simmons, value=Salary Employee relationship with Windtree Therapeutics Please note: 2014 to present Added 04/14/2022 by Steven Simonson, value=Salary