Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients. TRAUMADORNASE will be an institution-led, multicentre, double-blinded, placebo-controlled randomized trial in ventilated trauma patients. The primary trial objective is to demonstrate a reduction in the incidence of moderate-to-severe hypoxaemia in severe trauma patients during the first 7 days from 45% to 30% by providing aerosolized dornase alfa as compared to placebo. The secondary objectives are to demonstrate an improvement in lung function and a reduction in morbidity and mortality. Randomization of 250 patients per treatment arm will be carried out through a secure, web-based system. Statistical analyses will include a descriptive step and an inferential step using fully Bayesian techniques. The study was approved by both the Agence Nationale de la Sécurité du Médicament et des Produits de Santé (ANSM, on 5 October 2018) and a National Institutional Review Board (CPP, on 6 November 2018). Participant recruitment began in March 2019. Results will be published in international peer-reviewed medical journals. If early administration of inhaled dornase alfa actually reduces the incidence of moderate-to-severe hypoxaemia in patients with severe trauma, this new therapeutic strategy may be easily implemented in many clinical trauma care settings. This treatment may facilitate ventilator weaning, reduce the burden of trauma-induced lung inflammation and facilitate recovery and rehabilitation in severe trauma patients. ClinicalTrials.gov, NCT03368092. Registered on 11 December 2017.

中文翻译：

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TRAUMADORNASE方案：前瞻性，随机，多中心，双盲，安慰剂对照的雾化氧化酶阿尔法降低通气性创伤患者中低度至重度低氧血症发生率的临床试验

严重的创伤后，急性呼吸窘迫综合征继续导致明显的发病率和死亡率。根据柏林的定义，创伤引起的中度至重度低氧血症的发生率可能高达45％。其病理生理学包括释放损伤相关分子模式（DAMP），该模式通过触发嗜中性白细胞胞外陷阱（NETs）传播组织损伤。NETs包含涂有细胞质蛋白的DNA骨架，可驱动肺部细胞毒性作用。NET和许多DAMP的结构包括双链DNA，可防止血浆中和。Dornase alfa是美国食品药品监督管理局批准的重组DNase，可裂解细胞外DNA，因此可能破坏NETs和DAMPs的骨架。在实验模型中，雾化的脱氧核糖核酸酶可减少创伤引起的肺损伤并改善通气患者的动脉氧合。TRAUMADORNASE将是一项由机构主导的，多中心，双盲，安慰剂对照的通气性创伤患者随机试验。主要试验目的是通过与安慰剂相比，提供雾化的脱氧核糖核酸酶来证明重症创伤患者在前7天中度至重度低氧血症的发生率从4​​5％降低到30％。次要目标是证明肺功能得到改善，发病率和死亡率降低。每个治疗组将通过安全的基于网络的系统对250名患者进行随机分组。统计分析将包括使用完全贝叶斯技术的描述性步骤和推论性步骤。这项研究得到了国防和民族事务局（ANSM，2018年10月5日）和国家机构审查委员会（CPP，2018年11月6日）的批准。参加者招募于2019年3月开始。结果将在国际同行评审的医学期刊上发表。如果尽早服用吸入的氧化酶Alfa确实减少了严重创伤患者中中度至重度低氧血症的发生率，那么这种新的治疗策略可能会在许多临床创伤护理环境中轻松实施。这种治疗可以促进呼吸机的断奶，减轻创伤引起的肺部炎症的负担，并促进严重创伤患者的康复和康复。临床试验。政府，NCT03368092。2017年12月11日注册。