Study objectives: Primary objective: To compare the treatment effect of aerosolized DNase I to that of placebo (NaCl, 0.9%) on time to cessation of oxygen therapy or discharge from hospital in hospitalized patients with COVID-19 and respiratory dysfunction.~Secondary objectives: To compare the treatment effect of aerosolized DNase I to that of placebo (NaCl, 0.9%) on 28-day mortality, days alive and without ventilator treatment, days alive and without high flow nasal oxygen treatment (Optiflow), length of stay in the ICU, days alive and outside hospital, relapse of hypoxia, days alive and without need for supplemental oxygen, adverse reactions.~Exploratory objectives: To compare the treatment effect of aerosolized DNase I to that of placebo (NaCl, 9%) on quantification of NETs in respiratory secretions and on the incidence of clinical thromboembolic events.~Study design: Phase 2 open-label randomized controlled multicentre trial. The study period is 28 days from randomization. A long term follow-up on mortality and readmission will also be collected via patient medical records/registries at day 90, day 180, and day 360 after randomization.
Recent observations have suggested a role of neutrophil extracellular traps (NETs) in the pathophysiology of severe COVID-19. The aim of the study is to assess efficacy and safety of aerosolized DNase I to remove NETs and decrease respiratory distress in patients with COVID-19.