Importance Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration ClinicalTrials.gov Identifier: NCT02517489.

中文翻译：

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氢化可的松对 COVID-19 危重患者 21 天死亡率或呼吸支持的影响


重要性 2019 年冠状病毒病 (COVID-19) 与严重的肺部损伤有关。皮质类固醇是一种可能的治疗选择。目的 确定氢化可的松对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染并急性呼吸衰竭的危重患者第 21 天治疗失败的影响。设计、设置和参与者 在法国进行的多中心随机双盲序贯试验，每 50 名患者计划进行中期分析。 2020 年 3 月 7 日至 6 月 1 日期间入组因 COVID-19 相关急性呼吸衰竭入住重症监护病房 (ICU) 的患者，最后一次随访时间为 2020 年 6 月 29 日。该研究打算招募 290 名患者，但根据数据和安全监测委员会的建议提前停止。干预措施 患者被随机分配接受低剂量氢化可的松 (n = 76) 或安慰剂 (n = 73)。主要结果和措施 主要结果（第 21 天治疗失败）定义为死亡或持续依赖机械通气或高流量氧疗。预先设定的次要结局包括是否需要气管插管（基线时未插管的患者）；俯卧位、体外膜氧合和吸入一氧化氮的累积发生率（直到第 21 天）；从第 1 天到第 7 天，然后在第 14 天和第 21 天每天测量 Pao2:Fio2 比率；以及 ICU 住院期间继发感染的患者比例。结果 研究在 149 名患者（平均年龄 62.2 岁；30.2% 女性；81.2% 机械通气）入组后停止。一百四十八名患者（99.3%）完成了研究，共有69例治疗失败事件，其中氢化可的松组有11例死亡，安慰剂组有20例死亡。主要结局为第 21 天治疗失败，氢化可的松组 76 名患者中有 32 名 (42.1%) 发生，而安慰剂组 73 名患者中有 37 名 (50.7%) 发生（比例差异，-8.6% [95.48% CI， -24.9% 至 7.7%]；P = .29)。在 4 个预先指定的次要结果中，没有一个显示出显着差异。没有与研究治疗相关的严重不良事件。结论和相关性 在这项针对患有 COVID-19 并急性呼吸衰竭的危重患者的研究中，与安慰剂相比，低剂量氢化可的松并没有显着减少第 21 天的治疗失败（定义为死亡或持续呼吸支持）。研究提前停止，可能不足以发现主要结果的统计学和临床​​上的重要差异。试验注册 ClinicalTrials.gov 标识符：NCT02517489。