Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19 The CoDEX Randomized Clinical Trial
Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19 The CoDEX Randomized Clinical Trial
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DOI：
10.1001/jama.2020.17021
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发表时间：
2020-10-06
影响因子：
120.7
通讯作者：
Azevedo, Luciano C. P.
中科院分区：
文献类型：
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作者：
Tomazini, Bruno M.;Maia, Israel S.;Azevedo, Luciano C. P.
2019冠状病毒病（COVID-19）导致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。地塞米松的使用可能会减轻这些patients. Objective肺损伤，以确定是否静脉注射地塞米松增加呼吸机的天数与COVID-19相关的ARDS.DESIGN，设置和参与者在41个重症监护病房（ICU）在巴西进行的多中心，随机，开放标签，临床试验。根据柏林定义，2020年4月17日至6月23日入组了COVID-19和中重度ARDS患者。最终随访于2020年7月21日完成。在达到350名患者的计划样本量之前，在相关研究发表后，该试验提前停止。干预每天静脉注射20 mg地塞米松，持续5天，每天10 mg地塞米松，持续5天或直到ICU出院，加标准护理（n = 151）或单独标准护理（n = 148）。主要结果和测量主要结果是在最初28天内无呼吸机的天数，定义为活着并且没有机械通气。次要结局为28天时的全因死亡率，第15天时患者的临床状态（使用6分顺序量表）（范围从1，未住院到6，死亡），前28天内的无ICU天数，28天的机械通气持续时间和序贯器官衰竭评估（SOFA）评分（范围0-24，分数越高表示器官功能障碍越严重）。结果：共299名患者（平均[SD]年龄61 [14]岁; 37%为女性）入组，所有患者均完成随访。随机分配至地塞米松组的患者在前28天内平均无呼吸机天数为6.6天（95% CI，5.0-8.2），而标准治疗组为4.0天（95% CI，2.9-5.4）（差异为2.26; 95% CI，0.2-4.38; P = 0.04）。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），标准治疗组为7.5（95% CI，6.9-8.1）（差异，-1.16; 95% CI，-1.94至-0.38; P = 0.004）。在28天的全因死亡率、前28天的无ICU天数、28天的机械通气持续时间或15天的6点顺序量表的预定次要结局方面没有显著差异。33例患者地塞米松组为21.9%，（29.1%）在标准治疗组发生继发感染，47（31.1%）vs 42（28.3%）需要胰岛素控制血糖，和5（3.3%）vs 9（6.1%）发生其他严重不良事件。结论和相关性在COVID-19和中度或重度ARDS患者中，与单独标准护理相比，使用静脉内地塞米松加标准护理导致28天内无呼吸机天数（存活和无机械通气天数）的统计学显著增加。
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.