Importance Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS. Design, Setting, and Participants Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration ClinicalTrials.gov Identifier: NCT04327401.

中文翻译：

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地塞米松对中度或重度急性呼吸窘迫综合征和 COVID-19 患者无呼吸机生存天数的影响


重要性 2019 年冠状病毒病 (COVID-19) 引起的急性呼吸窘迫综合征 (ARDS) 与大量死亡率和医疗资源的使用有关。使用地塞米松可能会减轻这些患者的肺损伤。目的 确定静脉注射地塞米松是否会增加 COVID-19 相关 ARDS 患者的无需呼吸机的天数。设计、设置和参与者 在巴西 41 个重症监护病房 (ICU) 中进行的多中心、随机、开放标签临床试验。根据柏林定义，患有 COVID-19 和中度至重度 ARDS 的患者于 2020 年 4 月 17 日至 6 月 23 日入组。最终随访于 2020 年 7 月 21 日完成。该试验在相关研究发表后提前停止。在达到 350 名患者的计划样本量之前进行研究。干预措施 每天静脉注射 20 毫克地塞米松，持续 5 天，每天 10 毫克地塞米松，持续 5 天或直至出 ICU，加上标准护理 (n = 151) 或单独标准护理 (n = 148)。主要结果和措施 主要结果是前 28 天内的无呼吸机天数，定义为活着并且没有机械通气。次要结局是 28 天时的全因死亡率、第 15 天时使用 6 点顺序量表的患者临床状态（范围从 1（未住院）到 6（死亡））、前 28 天内无需 ICU 的天数、机械通气28 天时的持续时间，以及 48 小时、72 小时和 7 天时的序贯器官衰竭评估 (SOFA) 评分（范围为 0-24，分数越高表示器官功能障碍越严重）。结果 共有 299 名患者（平均 [SD] 年龄，61 [14] 岁；37% 女性）入组并全部完成随访。随机分配到地塞米松组的患者平均数为 6。前 28 天内有 6 天无呼吸机使用天数 (95% CI, 5.0-8.2)，而标准护理组有 4.0 天无呼吸机使用天数 (95% CI, 2.9-5.4)（差异为 2.26；95% CI, 0.2- 4.38；P = .04)。第 7 天时，地塞米松组患者的平均 SOFA 评分为 6.1（95% CI，5.5-6.7），而标准护理组患者的平均 SOFA 评分为 7.5（95% CI，6.9-8.1）（差异为 -1.16；95% CI） ，-1.94 至 -0.38；P = .004)。 28 天全因死亡率、前 28 天的无 ICU 天数、28 天的机械通气持续时间或 15 天的 6 点序数量表等预先设定的次要结局没有显着差异。地塞米松组有 33 名患者 (21.9%) 经历了继发感染，标准治疗组有 43 名患者 (29.1%) 出现继发感染，47 名患者 (31.1%) 和 42 名患者 (28.3%) 需要胰岛素控制血糖，5 名患者 (3.3%) vs 9 人 (6.1%) 经历过其他严重不良事件。结论和相关性 在患有中度或重度 ARDS 的 COVID-19 患者中，与单独使用标准护理相比，使用静脉注射地塞米松加标准护理可导致不使用呼吸机的天数（存活且不使用机械通气的天数）显着增加，具有统计学意义超过28天。试验注册 ClinicalTrials.gov 标识符：NCT04327401。