JMIR Publications

ABSTRACT

Background:

One unique feature of COVID-19-associated acute respiratory distress syndrome (ARDS) was surfactant deficiency because COVID-19 virus specifically attacks alveolar Type 2 cells.

Objective:

To evaluate the effects of a synthetic surfactant (lucinactant) therapy in COVID-19 ARDS patients.

Methods:

This open-label multicenter phase 1/2A trial enrolled adult COVID-19 ARDS patients who were within 7 days of mechanical ventilation (MV). Lucinactant (160 ml or ~80 mg total phospholipid/kg lean body weight) was delivered intratracheally. One retreatment was allowed at ≥ 6-hour intervals. The primary end points were oxygenation index (OI) and P/F through day 5 post-dosing. Other endpoints included time to deliver lucinactant, and respiratory system compliance (CRS). We monitored peri-dosing events and adverse events through 30 days post-dosing.

Results:

19 subjects were enrolled (14 receiving one dose and 5 receiving 2 doses). The mean age was 49 years. The mean time to administer lucinactant was 31 minutes. No significant changes were observed in OI (10.4±5.8 at baseline, 5.7±2.4 on day 5) or P/F (193±69 at baseline, 223±105 on day 5). CRS tended to improve between day 5 (55.4±18.5 ml/cmH2O) and baseline (40.7±17.8 ml/H2O)(p=0.10). Seven subjects (37%) died (6 from secondary infection and sepsis >13 days after dosing). Three subjects experienced transient peri-dosing desaturation or surfactant regurgitation.

Conclusions:

Our study showed intratracheal instillation of 1-2 doses of lucinactant in COVID-19 ARDS was generally well tolerated. Oxygenation parameters were stable. CRS tended to improve. The data supports further studies of lucinactant in ARDS patients with severe surfactant dysfunction. Clinical Trial: ClinicalTrials.Gov (NCT04389671)