Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19 A Randomized Clinical Trial
Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19 A Randomized Clinical Trial
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DOI：
10.1001/jama.2020.16761
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发表时间：
2020-10-06
影响因子：
120.7
通讯作者：
Le Gouge, Amelie
中科院分区：
文献类型：
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作者：
Dequin, Pierre-Francois;Heming, Nicholas;Le Gouge, Amelie
重要性2019年冠状病毒病(新冠肺炎)与严重的肺损伤有关。皮质类固醇是一种可能的治疗选择。目的探讨氢化可的松对严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染合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例患者进行中期分析。患者入选时间为2020年3月7日至6月1日，最后一次随访时间为2020年6月29日。这项研究打算招募290名患者，但在数据和安全监测委员会的建议下提前停止。干预患者随机接受小剂量氢化可的松(n=76)或安慰剂(n=73)。主要结果和衡量主要结果，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。预先指定的次要结果包括：是否需要气管插管(在基线未插管的患者中)；俯卧位、体外膜氧合和吸入一氧化氮的累积发生率(至第21天)；从第1天到第7天，然后是第14天和第21天每天测量的PaO2/FiO2比率；以及在ICU期间发生继发感染的患者比例。结果149名患者(平均年龄62.2岁；女性30.2%；机械通气81.2%)纳入研究后停止研究。148名患者(99.3%)完成了这项研究，共有69例治疗失败事件，其中氢化可的松组11例死亡，安慰剂组20例死亡。氢化可的松组76名患者中有32名(42.1%)在第21天出现治疗失败，而安慰剂组73名患者中有37名(50.7%)(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，没有一个显示出显著差异。没有与研究治疗相关的严重不良事件。结论和相关性：在这项研究中，与安慰剂相比，小剂量氢化可的松与安慰剂相比，没有显著减少第21天的治疗失败(定义为死亡或持续呼吸支持)。然而，这项研究很早就停止了，很可能没有能力在主要结果中找到统计上和临床上重要的差异。
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.