Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials
Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials
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DOI：
10.1186/s13063-020-04641-3
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发表时间：
2020-08-24
期刊：
影响因子：
2.5
通讯作者：
Marshall, John C.
中科院分区：
文献类型：
--
作者：
Sterne, Jonathan A. C.;Diaz, Janet;Marshall, John C.
目的：主要目的：评估与常规治疗或安慰剂相比，皮质类固醇对随机分组后 28 天内死亡率的影响。次要目标：研究与常规治疗或安慰剂相比，皮质类固醇对随机分组后 28 天之内死亡率的影响是否因亚组之间与治疗特征、随机分组时疾病严重程度、患者特征或偏倚风险相关而存在差异。旨在检查皮质类固醇与常规治疗或安慰剂相比对严重不良事件的影响。研究设计：随机对照试验的前瞻性荟萃分析。安慰剂对照试验和开放标签试验均符合资格。受试者：疑似或确诊的 COVID-19 住院危重患者。干预和比较：干预组将在随机分组后立即接受治疗剂量的类固醇（地塞米松、氢化可的松或甲泼尼龙）静脉注射或口服给药。比较组将接受标准护理或常规护理或 安慰剂。主要结局：随机分组后28天内的全因死亡率。检索方法：系统检索EudraCT、WHO ISRCTN注册中心和中国临床试验注册中心。此外，研究机构和 WHO 网络将被要求进行相关试验。偏倚风险评估：这些将基于 Cochrane RoB 2 工具，并将使用试验研究人员在为此前瞻性荟萃分析设计的表格上提供的结构化信息。研究结果摘要：我们将使用 GRADE 来评估证据的确定性。统计分析：试验研究人员将提供根据干预措施经历和未经历每种结果的参与者数量的数据 组、总体和指定子组。我们将进行固定效应（主要分析）和随机效应（Paule-Mandel 异质性估计和 Hartung-Knapp 调整）荟萃分析。我们将使用 I(2) 统计量来量化试验之间效果的不一致。亚组效应的证据将通过比较亚组效应的比值比以及相应的交互作用 p 值来量化。将使用随机效应元回归对试验特征定义的亚组进行比较。将通过估计试验特定的比值比比较亚组之间的干预效果，然后使用随机效应荟萃分析将这些效果结合起来，从而对由患者特征定义的亚组之间进行比较。根据剂量是否大于或小于或等于每天 400 毫克氢化可的松或等效剂量，类固醇干预将分为高剂量或低剂量。我们将使用网络荟萃分析方法来比较高剂量和低剂量类固醇干预的效果（因为一项试验将参与者随机分配到低剂量和高剂量类固醇组）。PROSPERO 注册号 CRD42020197242 完整方案：此前瞻性荟萃分析的完整方案作为附加文件附加，可从试验网站访问（附加文件1）。为了加快该材料的传播，熟悉的格式已被消除；这封信是系统评价完整方案关键要素的总结。
Objectives: Primary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events.Study design: Prospective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible.Participants: Hospitalised, critically ill patients with suspected or confirmed COVID-19.Intervention and comparator: Intervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization.The comparator groups will have received standard of care or usual care or placebo.Main outcome: All-cause mortality up to 28 days after randomization.Search methods: Systematic searching of, EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials.Risk of bias assessments: These will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis.Summary of findings: We will use GRADE to assess the certainty of the evidence.Statistical analyses: Trial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I(2)statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms).PROSPERO registration number CRD42020197242Full protocol: The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file1). To expedite dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol for the systematic review.