Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma
Status:
Recruiting
Trial end date:
2024-09-01
Target enrollment:
Participant gender:
Summary
Severe hypoxemia following trauma may happen in many circumstances (aspiration,
ventilation-associated pneumonia, lung contusion...), most of which are not exclusively
associated with a direct injury to the lungs. Severe trauma and associated musculoskeletal
injuries result in the acute release of Damage-Associated Molecular Patterns (DAMPs) in
plasma, many of which are made of nucleic acids. DAMPs then bind leukocytes and trigger
NETosis (Neutrophil Extracellular Traps), the release of nuclear material coated with
proteolytic enzymes, which ultimately promotes remote lung injury and acute respiratory
distress syndrome (ARDS).
Considering that many DAMPs and all NETs are made of nucleic acids, we hypothesize that
dornase alfa, a commercially available recombinant desoxyribonuclease (DNAse) could reduce
DAMPs and NETs-induced lung injury in severe trauma patients under mechanical ventilation in
the intensive care unit (ICU).
The primary objective is to demonstrate a reduction in the incidence of moderate to severe
ARDS in severe trauma patients during the first seven ICU days from 45% to 30% by providing
aerosolized dornase alfa once during the first two consecutive ICU days and compared to
equivalent provision of placebo (NaCl 0,9%).
The secondary objectives are to demonstrate, by using aerosolized dornase alfa compared to
placebo:
- an improvement in static lung compliance
- a reduction in mechanical ventilation duration / an increase in ventilation-free ICU
days
- a reduction in the length of ICU stay
- a reduction in the hospital length of stay
- a reduction in multi-organ failure
- a reduction in ventilator-associated pneumonia (VAP)
- a reduction in mortality at day 28