Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data

Introduction 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-analy...

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Main Authors: Yaseen Arabi, Sylvie Chevret, Laurent Billot, Anthony Gordon, Didier Keh, Romain Pirracchio, Balasubramanian Venkatesh, Djillali Annane, Andre Waschka, Jeremy Cohen, Simon Finfer, Naomi Hammond, John Myburgh, Anthony Delaney, Pierre Edouard Bollaert, Josef Briegel, Ling Liu, G Umberto, Liliana Mirea, L Charles, Nejla Tilouche, Surat Tongyoo, Ruiqiang Zheng
Format: Article
Language:English
Published: BMJ Publishing Group 2020-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/12/e040931.full
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author Yaseen Arabi
Sylvie Chevret
Laurent Billot
Anthony Gordon
Didier Keh
Romain Pirracchio
Balasubramanian Venkatesh
Djillali Annane
Andre Waschka
Jeremy Cohen
Simon Finfer
Naomi Hammond
John Myburgh
Anthony Delaney
Pierre Edouard Bollaert
Josef Briegel
Ling Liu
G Umberto
Liliana Mirea
L Charles
Nejla Tilouche
Surat Tongyoo
Ruiqiang Zheng
author_facet Yaseen Arabi
Sylvie Chevret
Laurent Billot
Anthony Gordon
Didier Keh
Romain Pirracchio
Balasubramanian Venkatesh
Djillali Annane
Andre Waschka
Jeremy Cohen
Simon Finfer
Naomi Hammond
John Myburgh
Anthony Delaney
Pierre Edouard Bollaert
Josef Briegel
Ling Liu
G Umberto
Liliana Mirea
L Charles
Nejla Tilouche
Surat Tongyoo
Ruiqiang Zheng
author_sort Yaseen Arabi
collection DOAJ
description Introduction 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.Methods and analysis 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.Ethics and dissemination 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.PROSPERO registration number CRD42017062198.
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spelling doaj-art-47c58406ed8142dfb1db7256d612fe002024-11-22T14:15:08ZengBMJ Publishing GroupBMJ Open2044-60552020-12-01101210.1136/bmjopen-2020-040931Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant dataYaseen Arabi0Sylvie Chevret1Laurent Billot2Anthony Gordon3Didier Keh4Romain Pirracchio5Balasubramanian Venkatesh6Djillali Annane7Andre Waschka8Jeremy Cohen9Simon Finfer10Naomi Hammond11John Myburgh12Anthony Delaney13Pierre Edouard BollaertJosef BriegelLing Liu14G UmbertoLiliana MireaL CharlesNejla TiloucheSurat TongyooRuiqiang Zheng12 Intensive Care Department, King Abdullah International Medical Research Center, Riyadh, Saudi ArabiaSaint Louis University Hospital, Department of Biostatistics, Paris, France10 The George Institute for Global Health, University of New South Wales, Sydney, AustraliaSection of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UKattending physicianDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, USARoyal Brisbane and Women’s Hospital, Herston, Queensland, AustraliaIHU PROMETHEUS, General ICU, Raymond Poincaré Hospital, University Paris Saclay campus Versailles, APHP, Garches, FranceUniversity of California Berkeley, Berkeley, California, USAUniversity of Queensland, Brisbane, Queensland, Australia4 Critical Care Program, The George Institute for Global Health, Sydney, New South Wales, AustraliaGeorge Institute for Global Health, Camperdown, New South Wales, Australia7 The George Institute for Global Health, Newtown, New South Wales, AustraliaIntensive Care, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaDepartment of Ophthalmology, Chongqing Emergency Medical Center; Chongqing University Central Hospital, Chongqing University, Chongqing, ChinaIntroduction 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.Methods and analysis 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.Ethics and dissemination 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.PROSPERO registration number CRD42017062198.https://bmjopen.bmj.com/content/10/12/e040931.full
spellingShingle Yaseen Arabi
Sylvie Chevret
Laurent Billot
Anthony Gordon
Didier Keh
Romain Pirracchio
Balasubramanian Venkatesh
Djillali Annane
Andre Waschka
Jeremy Cohen
Simon Finfer
Naomi Hammond
John Myburgh
Anthony Delaney
Pierre Edouard Bollaert
Josef Briegel
Ling Liu
G Umberto
Liliana Mirea
L Charles
Nejla Tilouche
Surat Tongyoo
Ruiqiang Zheng
Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
BMJ Open
title Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
title_full Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
title_fullStr Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
title_full_unstemmed Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
title_short Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
title_sort effects of low dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock a protocol for a systematic review and meta analysis of individual participant data
url https://bmjopen.bmj.com/content/10/12/e040931.full
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