Villar Jesús, Belda Javier, Añón José Manuel, Blanco Jesús, Pérez-Méndez Lina, Ferrando Carlos, Martínez Domingo, Soler Juan Alfonso, Ambrós Alfonso, Muñoz Tomás, Rivas Rosana, Corpas Ruth, Díaz-Dominguez Francisco J, Soro Marina, García-Bello Miguel Angel, Fernández Rosa Lidia, Kacmarek Robert M
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, 4th floor - South Wing, 35019, Las Palmas de Gran Canaria, Spain.
Trials. 2016 Jul 22;17:342. doi: 10.1186/s13063-016-1456-4.
Although much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality.
METHODS/DESIGN: This is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment.
This study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS.
Registered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website ( NCT01731795 ).
尽管我们对急性呼吸窘迫综合征（ARDS）的发病机制及影响患者预后的因素已有很多认识进展，但ARDS仍无特效药物治疗。多项临床试验评估了皮质类固醇的效用，但由于样本量小、选择偏倚、患者异质性以及治疗开始时间或疗程持续时间等原因，均未显示出明确的益处。我们推测，静脉注射地塞米松辅助治疗持续性ARDS可能会改变肺部和全身炎症反应，从而降低发病率，减少机械通气时间并降低死亡率。
方法/设计：这是一项针对314例持续性中重度ARDS患者的前瞻性、多中心、随机对照试验。持续性ARDS定义为在常规重症监护24小时后，在呼气末正压（PEEP）≥10 cmH₂O且吸入氧浓度（FiO₂）≥0.5的情况下，动脉血氧分压（PaO₂）/FiO₂≤200 mmHg。符合条件的患者将被随机分为两组：（i）不使用地塞米松的常规治疗组，（ii）常规治疗加地塞米松组。地塞米松组患者从第1天至第5天每天静脉注射20 mg，从第6天至第10天每天静脉注射10 mg。主要结局是无呼吸机天数，定义为插管后第28天存活且未使用机械通气的天数。次要结局是入组后第60天的全因死亡率。
本研究将是评估地塞米松在持续性ARDS患者中作用的最大规模随机对照临床试验。
于2012年11月21日在ClinicalTrials.gov网站注册为DEXA-ARDS（NCT01731795）。
