Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis.
Journal
Acta anaesthesiologica Scandinavica
ISSN: 1399-6576
Titre abrégé: Acta Anaesthesiol Scand
Pays: England
ID NLM: 0370270
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
28
01
2021
accepted:
31
01
2021
pubmed:
15
2
2021
medline:
4
5
2021
entrez:
14
2
2021
Statut:
ppublish
Résumé
Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
Sections du résumé
BACKGROUND
Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia.
METHODS
This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors.
DISCUSSION
This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
Identifiants
pubmed: 33583027
doi: 10.1111/aas.13793
pmc: PMC8014670
doi:
Substances chimiques
Dexamethasone
7S5I7G3JQL
Banques de données
ClinicalTrials.gov
['NCT04509973']
Types de publication
Clinical Trial Protocol
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
702-710Subventions
Organisme : The Novo Nordisk Foundation
ID : 0062998
Organisme : Rigshospitalet's Research Council
ID : E-22703-06
Informations de copyright
© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Références
J Clin Epidemiol. 2005 Mar;58(3):261-8
pubmed: 15718115
BMJ. 2010 Mar 23;340:c332
pubmed: 20332509
Acta Anaesthesiol Scand. 2020 Oct;64(9):1365-1375
pubmed: 32779728
Clin Infect Dis. 2020 Apr 27;:
pubmed: 32338708
Stat Methods Med Res. 2016 Apr;25(2):538-52
pubmed: 23070590
Am J Respir Crit Care Med. 2020 Feb 15;201(4):423-429
pubmed: 31574228
Intensive Care Med. 2020 May;46(5):930-942
pubmed: 32072303
Ann Intern Med. 2013 Feb 5;158(3):200-7
pubmed: 23295957
Acta Anaesthesiol Scand. 2021 May;65(5):702-710
pubmed: 33583027
Acta Anaesthesiol Scand. 2019 Oct;63(9):1251-1256
pubmed: 31321771
Acta Anaesthesiol Scand. 2021 Jul;65(6):834-845
pubmed: 33583034
BMJ Open. 2019 Mar 7;9(3):e024256
pubmed: 30850406
Intensive Care Med. 2020 May;46(5):1087-1088
pubmed: 32189010
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Nature. 2019 Mar;567(7748):305-307
pubmed: 30894741
J Med Internet Res. 2018 Oct 24;20(10):e10873
pubmed: 30148453
Crit Care Med. 2019 Dec;47(12):1680-1691
pubmed: 31567349
BMJ. 2020 Sep 4;370:m3379
pubmed: 32887691
Eur J Epidemiol. 2016 Apr;31(4):337-50
pubmed: 27209009
Crit Care. 2017 Jun 5;21(1):132
pubmed: 28583149
Intensive Care Med. 2020 Apr;46(4):717-726
pubmed: 31938829
JAMA. 2020 Oct 6;324(13):1317-1329
pubmed: 32876697
JAMA. 2020 Oct 6;324(13):1330-1341
pubmed: 32876694
Intensive Care Med. 2020 Apr;46(4):793-795
pubmed: 32076767
BMJ. 1995 Aug 19;311(7003):485
pubmed: 7647644
JAMA. 2020 Jun 9;323(22):2256-2257
pubmed: 32383733
Transpl Int. 2020 Jan;33(1):50-55
pubmed: 31560143
J Clin Epidemiol. 2008 Apr;61(4):344-9
pubmed: 18313558
Lancet Respir Med. 2020 Mar;8(3):267-276
pubmed: 32043986
Ann Am Thorac Soc. 2020 Jul;17(7):879-891
pubmed: 32267771
Acta Anaesthesiol Scand. 2020 Oct;64(9):1376-1381
pubmed: 32659856