Clinical Research Directory

Inhaled Dornase Alpha to Reduce Respiratory Failure After Severe Trauma

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

ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients

The EPO-TRAUMA study is a prospective, multi-centre, double-blind, phase III, randomised controlled trial evaluating the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients. 2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.

Evolution of Oropharyngeal and Rectal Microbiota After Severe Traumatic Brain Injury

Modifications of the human gut microbiota have been associated with different pathological conditions such as obesity, inflammatory bowel diseases and neurodegenerative diseases. Recently the " Brain-Gut Axis ", a bidirectional communication axis between brain and gut, has been described. In recent animal studies, an acute brain injury was associated with rapid modifications of the gut microbiota. In humans, traumatic brain injury (TBI) is a leading cause of death and disability. The patterns of gut and oropharyngeal microbiota following TBI are unknown. The primary purpose of this study is to characterize gut and oropharyngeal microbiota of patients with severe TBI.