TY - JOUR
T1 - Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial
T2 - Protocol for a secondary Bayesian analysis
AU - Granholm, Anders
AU - Munch, Marie Warrer
AU - Myatra, Sheila Nainan
AU - Vijayaraghavan, Bharath Kumar Tirupakuzhi
AU - Cronhjort, Maria
AU - Wahlin, Rebecka Rubenson
AU - Jakob, Stephan M.
AU - Cioccari, Luca
AU - Kjær, Maj Brit Nørregaard
AU - Vesterlund, Gitte Kingo
AU - Meyhoff, Tine Sylvest
AU - Helleberg, Marie
AU - Møller, Morten Hylander
AU - Benfield, Thomas
AU - Venkatesh, Balasubramanian
AU - Hammond, Naomi
AU - Micallef, Sharon
AU - Bassi, Abhinav
AU - John, Oommen
AU - Jha, Vivekanand
AU - Kristiansen, Klaus Tjelle
AU - Ulrik, Charlotte Suppli
AU - Jørgensen, Vibeke Lind
AU - Smitt, Margit
AU - Bestle, Morten H.
AU - Andreasen, Anne Sofie
AU - Poulsen, Lone Musaeus
AU - Rasmussen, Bodil Steen
AU - Brøchner, Anne Craveiro
AU - Strøm, Thomas
AU - Møller, Anders
AU - Khan, Mohd Saif
AU - Padmanaban, Ajay
AU - Divatia, Jigeeshu Vasishtha
AU - Saseedharan, Sanjith
AU - Borawake, Kapil
AU - Kapadia, Farhad
AU - Dixit, Subhal
AU - Chawla, Rajesh
AU - Shukla, Urvi
AU - Amin, Pravin
AU - Chew, Michelle S.
AU - Gluud, Christian
AU - Lange, Theis
AU - Perner, Anders
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1111/aas.13793
DO - 10.1111/aas.13793
M3 - Journal article
C2 - 33583027
AN - SCOPUS:85101768138
VL - 65
SP - 702
EP - 710
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
SN - 0001-5172
IS - 5
ER -