Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19 A Meta-analysis
Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19 A Meta-analysis
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DOI：
10.1001/jama.2020.17023
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发表时间：
2020-10-06
影响因子：
120.7
通讯作者：
Marshall, John C.
中科院分区：
文献类型：
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作者：
Sterne, Jonathan A. C.;Murthy, Srinivas;Marshall, John C.
重要性 2019 年冠状病毒病 (COVID-19) 患者需要有效的治疗，临床试验数据表明，低剂量地塞米松可降低需要呼吸支持的 COVID-19 住院患者的死亡率。 目的 评估与常规治疗或安慰剂相比，皮质类固醇给药与 28 天全因死亡率之间的关联。 设计、设置和参与者 前瞻性荟萃分析 该研究汇集了 7 项随机临床试验的数据，这些试验评估了皮质类固醇对 1703 名 COVID-19 危重患者的疗效。这些试验于2020年2月26日至2020年6月9日在12个国家进行，最终随访日期为2020年7月6日。汇总数据来自各个试验的总体数据和预定义亚组。使用 Cochrane 偏倚风险评估工具评估偏倚风险。使用 I-2 统计数据评估试验结果之间的不一致。主要分析是对总体死亡率的反方差加权固定效应荟萃分析，使用比值比 (OR) 量化干预措施与死亡率之间的关联。还进行了随机效应荟萃分析（使用异质性的 Paule-Mandel 估计和 Hartung-Knapp 调整）以及使用风险比的反向方差加权固定效应分析。 暴露 患者被随机分配接受全身地塞米松、氢化可的松或甲泼尼龙（678 名患者）或接受常规护理或安慰剂（1025 主要结果和指标 主要结果指标是随机分组后 28 天的全因死亡率。次要结局是研究者定义的严重不良事件。 结果 共有 1703 名患者（中位年龄 60 岁[四分位距，52-68 岁]；488 名[29%] 女性）纳入分析。由于随机化方法的原因，7 项死亡率结果中有 6 项的偏倚风险被评估为“低”，而 1 项试验的偏倚风险被评估为“一些问题”。 5 项试验报告了 28 天时的死亡率，1 项试验报告了 21 天时的死亡率，1 项试验报告了 30 天时的死亡率。 678 名随机接受皮质类固醇治疗的患者中有 222 人死亡，1025 名随机接受常规治疗或安慰剂的患者中有 425 人死亡（总结 OR，0.66 [95% CI，0.53-0.82]；基于固定效应荟萃分析，P < .001）。试验结果（I-2 = 15.6%；异质性 P = .31）与基于随机效应荟萃分析的总结 OR 为 0.70（95% CI，0.48-1.01；P = .053）之间几乎没有不一致。与常规治疗或安慰剂（3 项试验，1282 例患者，527 例死亡）相比，地塞米松与死亡率相关的固定效应总结 OR 为 0.64（95% CI，0.50-0.82；P < .001），氢化可的松（3 项试验， 374 名患者，94 死亡），甲基泼尼松龙的 OR 为 0.91（95% CI，0.29-2.87；P = .87）（1 项试验，47 名患者，26 名死亡）。在报告严重不良事件的 6 项试验中，在 354 名随机接受皮质类固醇治疗的患者中发生了 64 起事件，在 342 名随机接受常规治疗或安慰剂的患者中发生了 80 起事件。 结论和相关性 在这项针对 COVID-19 危重患者的临床试验的前瞻性荟萃分析中，与常规治疗或安慰剂相比，全身性皮质类固醇的给药与较低的 28 天全因治疗相关 死亡率。
IMPORTANCE Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.OBJECTIVE To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.DESIGN, SETTING, AND PARTICIPANTS Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I-2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios.EXPOSURES Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).MAIN OUTCOMES AND MEASURES The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events.RESULTS A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I-2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo.CONCLUSIONS AND RELEVANCE In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.