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 trialKarolinska Inst, Sweden.
Karolinska Inst, Sweden.
Univ Bern, Switzerland.
Univ Bern, Switzerland.
Copenhagen Univ Hosp, Denmark; Collaborat Res Intens Care CRIC, Denmark.
Copenhagen Univ Hosp, Denmark; Collaborat Res Intens Care CRIC, Denmark.
Copenhagen Univ Hosp, Denmark; Collaborat Res Intens Care CRIC, Denmark.
Univ Copenhagen, Denmark.
Copenhagen Univ Hosp, Denmark; Collaborat Res Intens Care CRIC, Denmark.
Univ Copenhagen, Denmark.
Univ New Southern Wales, Australia.
Univ New Southern Wales, Australia; Royal North Shore Hosp, Australia.
Univ New Southern Wales, Australia.
George Inst Global Hlth, India.
George Inst Global Hlth, India; Manipal Acad Higher Educ, India.
George Inst Global Hlth, India; Manipal Acad Higher Educ, India; Imperial Coll London, England.
Univ Copenhagen, Denmark.
Univ Copenhagen, Denmark.
Univ Copenhagen, Denmark.
Univ Copenhagen, Denmark.
Copenhagen Univ Hosp North Zealand, Denmark; Univ Copenhagen, Denmark.
Univ Copenhagen, Denmark.
Zealand Univ Hosp, Denmark.
Collaborat Res Intens Care CRIC, Denmark; Aalborg Univ Hosp, Denmark.
Collaborat Res Intens Care CRIC, Denmark; Univ Hosp Southern Denmark, Denmark.
Odense Univ Hosp, Denmark; Univ Hosp Southern, Denmark.
Ringsted Hosp, Denmark.
Rajendra Inst Med Sci, India.
Apollo Hosp, India.
Tata Mem Hosp, India.
SL Raheja Hosp, India.
Vishwaraj Hosp, India.
Hinduja Hosp, India.
Sanjeevan Hosp, India.
Indraprastha Apollo Hosp, India.
Symbiosis Univ Hosp, India.
Bombay Hosp & Med Res Ctr, India.
Bispebjerg Hosp, Denmark.
Copenhagen Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
Univ Copenhagen, Denmark.
Copenhagen Univ Hosp, Denmark; Collaborat Res Intens Care CRIC, Denmark.
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2022 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 48, no 1, p. 45-55Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
SPRINGER , 2022. Vol. 48, no 1, p. 45-55
Keywords [en]
COVID-19; Hypoxaemia; Critical illness; Corticosteroids; Bayesian analysis
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-181186DOI: 10.1007/s00134-021-06573-1ISI: 000716840800001PubMedID: 34757439OAI: oai:DiVA.org:liu-181186DiVA, id: diva2:1613438
Note
Funding Agencies|Novo Nordisk FoundationNovo Nordisk FoundationNovocure Limited [0062998]; Rigshospitalets Research Council [E-22703-06]
2021-11-222021-11-222022-03-14