Annane Djillali, Pirracchio Romain, Billot Laurent, Waschka Andre, Chevret Sylvie, Cohen Jeremy, Finfer Simon, Gordon Anthony, Hammond Naomi, Myburgh John, Venkatesh Balasubramanian, Delaney Anthony
School of Medicine, Versailles Saint-Quentin-en-Yvelines University, Versailles, Île-de-France, France
Universite Paris-Saclay, Saint-Aubin, Île-de-France, France.
BMJ Open. 2020 Dec 2;10(12):e040931. doi: 10.1136/bmjopen-2020-040931.
The benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placebo or usual care on 90-day mortality and other outcomes in patients with septic shock.
To assess the benefits and risks of hydrocortisone, with or without fludrocortisone for adults with septic shock, we will search major electronic databases from inception to September 2020 (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Latin American Caribbean Health Sciences Literature), complimented by a search for unpublished trials. The primary analysis will compare hydrocortisone with or without fludrocortisone to placebo or no treatment in adult patients with septic shock. Secondary analyses will compare hydrocortisone to placebo (or usual care), hydrocortisone plus fludrocortisone to placebo (or usual care), and hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome will be all cause mortality at 90 days. We will conduct both one-stage IPDMA using mixed-effect models and machine learning with targeted maximum likelihood analyses. We will assess the risk of bias related to unshared data and related to the quality of individual trial.
This IPDMA will use existing data from completed randomised clinical trials and will comply with the ethical and regulatory requirements regarding data sharing for each of the component trials. The findings of this study will be submitted for publication in a peer-review journal with straightforward policy for open access.
CRD42017062198.
在众多随机对照试验和试验水平的荟萃分析中，已对低剂量氢化可的松治疗感染性休克患者的益处和风险进行了研究。然而，这种治疗方法的常规使用仍存在争议。为克服以往使用汇总数据进行荟萃分析的局限性，我们将对氢化可的松联合或不联合氟氢可的松与安慰剂或常规治疗相比，对感染性休克患者90天死亡率及其他结局的影响进行个体患者数据荟萃分析（IPDMA）。
为评估氢化可的松联合或不联合氟氢可的松治疗成人感染性休克的益处和风险，我们将检索从开始到2020年9月的主要电子数据库（Cochrane对照试验中心注册库、MEDLINE、EMBASE和拉丁美洲加勒比卫生科学文献数据库），并辅以未发表试验的检索。主要分析将比较感染性休克成年患者中联合或不联合氟氢可的松的氢化可的松与安慰剂或不治疗的情况。次要分析将比较氢化可的松与安慰剂（或常规治疗）、氢化可的松加氟氢可的松与安慰剂（或常规治疗），以及氢化可的松与氢化可的松加氟氢可的松。主要结局将是90天全因死亡率。我们将使用混合效应模型和具有靶向最大似然分析的机器学习进行单阶段IPDMA。我们将评估与未共享数据以及个体试验质量相关的偏倚风险。
这项IPDMA将使用已完成的随机临床试验的现有数据，并将符合各组成试验数据共享的伦理和监管要求。本研究的结果将提交至同行评审期刊发表，并采用直接的开放获取政策。
PROSPERO注册号：CRD42017062198。
