tetano
Editor, Senior Moderator
Intensive Care Med
. 2021 Nov 10.
doi: 10.1007/s00134-021-06573-1. Online ahead of print.
Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
Anders Granholm[SUP] 1 2 [/SUP], Marie Warrer Munch[SUP] 3 4 [/SUP], Sheila Nainan Myatra[SUP] 5 [/SUP], Bharath Kumar Tirupakuzhi Vijayaraghavan[SUP] 6 7 8 [/SUP], Maria Cronhjort[SUP] 9 [/SUP], Rebecka Rubenson Wahlin[SUP] 9 [/SUP], Stephan M Jakob[SUP] 10 [/SUP], Luca Cioccari[SUP] 10 [/SUP], Maj-Brit Nørregaard Kjær[SUP] 3 4 [/SUP], Gitte Kingo Vesterlund[SUP] 3 4 [/SUP], Tine Sylvest Meyhoff[SUP] 3 4 [/SUP], Marie Helleberg[SUP] 11 [/SUP], Morten Hylander Møller[SUP] 3 4 [/SUP], Thomas Benfield[SUP] 12 [/SUP], Balasubramanian Venkatesh[SUP] 13 [/SUP], Naomi E Hammond[SUP] 13 14 [/SUP], Sharon Micallef[SUP] 13 [/SUP], Abhinav Bassi[SUP] 8 [/SUP], Oommen John[SUP] 8 15 [/SUP], Vivekanand Jha[SUP] 8 15 16 [/SUP], Klaus Tjelle Kristiansen[SUP] 17 [/SUP], Charlotte Suppli Ulrik[SUP] 18 [/SUP], Vibeke Lind Jørgensen[SUP] 19 [/SUP], Margit Smitt[SUP] 20 [/SUP], Morten H Bestle[SUP] 21 22 [/SUP], Anne Sofie Andreasen[SUP] 23 [/SUP], Lone Musaeus Poulsen[SUP] 24 [/SUP], Bodil Steen Rasmussen[SUP] 4 25 [/SUP], Anne Craveiro Brøchner[SUP] 4 26 [/SUP], Thomas Strøm[SUP] 27 28 [/SUP], Anders Møller[SUP] 29 [/SUP], Mohd Saif Khan[SUP] 30 [/SUP], Ajay Padmanaban[SUP] 6 [/SUP], Jigeeshu Vasishtha Divatia[SUP] 5 [/SUP], Sanjith Saseedharan[SUP] 31 [/SUP], Kapil Borawake[SUP] 32 [/SUP], Farhad Kapadia[SUP] 33 [/SUP], Subhal Dixit[SUP] 34 [/SUP], Rajesh Chawla[SUP] 35 [/SUP], Urvi Shukla[SUP] 36 [/SUP], Pravin Amin[SUP] 37 [/SUP], Michelle S Chew[SUP] 38 [/SUP], Christian Aage Wamberg[SUP] 39 [/SUP], Christian Gluud[SUP] 40 41 [/SUP], Theis Lange[SUP] 42 [/SUP], Anders Perner[SUP] 3 4 [/SUP]
Affiliations
Abstract
Purpose: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation.
Methods: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone.
Results: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses.
Conclusion: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
Trial registration: ClinicalTrials.gov NCT04509973.
Keywords: Bayesian analysis; COVID-19; Corticosteroids; Critical illness; Hypoxaemia.
. 2021 Nov 10.
doi: 10.1007/s00134-021-06573-1. Online ahead of print.
Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
Anders Granholm[SUP] 1 2 [/SUP], Marie Warrer Munch[SUP] 3 4 [/SUP], Sheila Nainan Myatra[SUP] 5 [/SUP], Bharath Kumar Tirupakuzhi Vijayaraghavan[SUP] 6 7 8 [/SUP], Maria Cronhjort[SUP] 9 [/SUP], Rebecka Rubenson Wahlin[SUP] 9 [/SUP], Stephan M Jakob[SUP] 10 [/SUP], Luca Cioccari[SUP] 10 [/SUP], Maj-Brit Nørregaard Kjær[SUP] 3 4 [/SUP], Gitte Kingo Vesterlund[SUP] 3 4 [/SUP], Tine Sylvest Meyhoff[SUP] 3 4 [/SUP], Marie Helleberg[SUP] 11 [/SUP], Morten Hylander Møller[SUP] 3 4 [/SUP], Thomas Benfield[SUP] 12 [/SUP], Balasubramanian Venkatesh[SUP] 13 [/SUP], Naomi E Hammond[SUP] 13 14 [/SUP], Sharon Micallef[SUP] 13 [/SUP], Abhinav Bassi[SUP] 8 [/SUP], Oommen John[SUP] 8 15 [/SUP], Vivekanand Jha[SUP] 8 15 16 [/SUP], Klaus Tjelle Kristiansen[SUP] 17 [/SUP], Charlotte Suppli Ulrik[SUP] 18 [/SUP], Vibeke Lind Jørgensen[SUP] 19 [/SUP], Margit Smitt[SUP] 20 [/SUP], Morten H Bestle[SUP] 21 22 [/SUP], Anne Sofie Andreasen[SUP] 23 [/SUP], Lone Musaeus Poulsen[SUP] 24 [/SUP], Bodil Steen Rasmussen[SUP] 4 25 [/SUP], Anne Craveiro Brøchner[SUP] 4 26 [/SUP], Thomas Strøm[SUP] 27 28 [/SUP], Anders Møller[SUP] 29 [/SUP], Mohd Saif Khan[SUP] 30 [/SUP], Ajay Padmanaban[SUP] 6 [/SUP], Jigeeshu Vasishtha Divatia[SUP] 5 [/SUP], Sanjith Saseedharan[SUP] 31 [/SUP], Kapil Borawake[SUP] 32 [/SUP], Farhad Kapadia[SUP] 33 [/SUP], Subhal Dixit[SUP] 34 [/SUP], Rajesh Chawla[SUP] 35 [/SUP], Urvi Shukla[SUP] 36 [/SUP], Pravin Amin[SUP] 37 [/SUP], Michelle S Chew[SUP] 38 [/SUP], Christian Aage Wamberg[SUP] 39 [/SUP], Christian Gluud[SUP] 40 41 [/SUP], Theis Lange[SUP] 42 [/SUP], Anders Perner[SUP] 3 4 [/SUP]
Affiliations
- PMID: 34757439
- DOI: 10.1007/s00134-021-06573-1
Abstract
Purpose: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation.
Methods: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone.
Results: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses.
Conclusion: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
Trial registration: ClinicalTrials.gov NCT04509973.
Keywords: Bayesian analysis; COVID-19; Corticosteroids; Critical illness; Hypoxaemia.