Lucinactant, a Synthetic Surfactant for the Treatment of Acute Respiratory Distress Syndrome Caused by COVID-19: Phase 1/2A Trial
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract Background One unique feature of COVID-19–associated acute respiratory distress syndrome (ARDS) is surfactant deficiency because SARS-CoV-2 specifically attacks alveolar type 2 cells. Objective In this study, we evaluated the effects of a synthetic surfactant (lucinactant) therapy in patients with COVID-19–associated ARDS. Methods This open-label multicenter phase 1/2A trial enrolled adult patients with COVID-19–associated ARDS who were within 7 days of mechanical ventilation initiation. Lucinactant (160 mL or approximately 80 mg of total phospholipids per kilogram of lean body weight) was delivered intratracheally. One retreatment was allowed at ≥6-hour intervals. The primary end points were oxygenation index and PO-to–fraction of inspired oxygen ratio up to day 5 after dosing. Other end points included time to deliver lucinactant and respiratory system compliance (C). We monitored peridosing events and adverse events up to 30 days after dosing. Results A total of 19 treated patients were enrolled (n=14, 73.7% receiving 1 dose; n=5, 26.3% receiving 2 doses). The mean age was 49 (SD 15) years. The mean time to administer lucinactant was 31 minutes. No significant changes were observed in oxygenation index (mean 10.4, SD 5.8 at baseline; 8.6, SD 2.7 at 12 hours; and 5.7, SD 2.4 on day 5;=.12 via ANOVA) or PO-to–fraction of inspired oxygen ratio (mean 193, SD 69 at baseline; mean 179, SD 57 at 12 hours; and mean 223, SD 105 on day 5;=.44 via ANOVA). Calso did not chang
Abstract
Abstract Background One unique feature of COVID-19–associated acute respiratory distress syndrome (ARDS) is surfactant deficiency because SARS-CoV-2 specifically attacks alveolar type 2 cells. Objective In this study, we evaluated the effects of a synthetic surfactant (lucinactant) therapy in patients with COVID-19–associated ARDS. Methods This open-label multicenter phase 1/2A trial enrolled adult patients with COVID-19–associated ARDS who were within 7 days of mechanical ventilation initiation. Lucinactant (160 mL or approximately 80 mg of total phospholipids per kilogram of lean body weight) was delivered intratracheally. One retreatment was allowed at ≥6-hour intervals. The primary end points were oxygenation index and PO-to–fraction of inspired oxygen ratio up to day 5 after dosing. Other end points included time to deliver lucinactant and respiratory system compliance (C). We monitored peridosing events and adverse events up to 30 days after dosing. Results A total of 19 treated patients were enrolled (n=14, 73.7% receiving 1 dose; n=5, 26.3% receiving 2 doses). The mean age was 49 (SD 15) years. The mean time to administer lucinactant was 31 minutes. No significant changes were observed in oxygenation index (mean 10.4, SD 5.8 at baseline; 8.6, SD 2.7 at 12 hours; and 5.7, SD 2.4 on day 5;=.12 via ANOVA) or PO-to–fraction of inspired oxygen ratio (mean 193, SD 69 at baseline; mean 179, SD 57 at 12 hours; and mean 223, SD 105 on day 5;=.44 via ANOVA). Calso did not change significantly (mean 40.7, SD 17.8 mL/HO at baseline; mean 33.6, SD 8.5 mL/HO at 12 hours; and mean 55.4, SD 18.5 mL/cmHO on day 5;=.12 via ANOVA). A total of 36.8% (n=7) of the participants died (6 from secondary infection and sepsis >13 days after dosing). In total, 15.8% (n=3) of the patients experienced transient peridosing desaturation or surfactant regurgitation. Conclusions Our study showed that intratracheal instillation of 1 to 2 doses of lucinactant in COVID-19–associated ARDS was generally well tolerated. There were no significant changes in oxygenation parameters or C. The data suggest that, when future studies of lucinactant in patients with ARDS with severe surfactant dysfunction are conducted, an earlier and longer treatment protocol using different delivery methods that reach a larger alveolar surface area, such as aerosolization, may be needed to yield any beneficiary effects.