Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial

Annals of Intensive Care

Research

Chevret Sylvie¹  Timsit Jean-François²  Bouadma Lila²  Burdet Charles³  Dupuis Claire⁴ 

[1] ECSTRRA, UMR 1153, Saint Louis Hospital, University Paris Cité, Paris, France;Medical and Infectious Diseases ICU, APHP Bichat Hospital, 75018, Paris, France;Université Paris Cité, IAME, INSERM, UMR 1137, 75018, Paris, France;Université Paris Cité, IAME, INSERM, UMR 1137, 75018, Paris, France;Epidemiology, Biostatistics and Clinical Research Department, AP-HP, Bichat Hospital, 75018, Paris, France;Université Paris Cité, IAME, INSERM, UMR 1137, 75018, Paris, France;Intensive Care Unit, Gabriel Montpied Hospital, CHU de Clermont-Ferrand, 63000, Clermont-Ferrand, France;

关键词: SARS-Cov-2;    Steroids;    Dose;    Sepsis;    Acute respiratory failure;    Remdesivir;    Critical care;    ARDS;    Bayesian analysis;    Interaction;   

DOI  :  10.1186/s13613-023-01168-z

 received in 2023-05-08, accepted in 2023-07-31,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe respective benefits of high and low doses of dexamethasone (DXM) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and acute respiratory failure (ARF) are controversial, with two large triple-blind RCTs reaching very important difference in the effect-size. In the COVIDICUS trial, no evidence of additional benefit of high-dose dexamethasone (DXM20) was found. We aimed to explore whether some specific patient phenotypes could benefit from DXM20 compared to the standard of care 6 mg dose of DXM (DXMSoC).MethodsWe performed a post hoc exploratory Bayesian analysis of 473 patients who received either DXMSoc or DXM20 in the COVIDICUS trial. The outcome was the 60 day mortality rate of DXM20 over DXMSoC, with treatment effect measured on the hazard ratio (HR) estimated from Cox model. Bayesian analyses allowed to compute the posterior probability of a more than trivial benefit (HR < 0.95), and that of a potential harm (HR > 1.05). Bayesian measures of interaction then quantified the probability of interaction (Pr Interact) that the HR of death differed across the subsets by 20%. Primary analyses used noninformative priors, centred on HR = 1.00. Sensitivity analyses used sceptical and enthusiastic priors, based on null (HR = 1.00) or benefit (HR = 0.95) effects.ResultsOverall, the posterior probability of a more than trivial benefit and potential harm was 29.0 and 51.1%, respectively. There was some evidence of treatment by subset interaction (i) according to age (Pr Interact, 84%), with a 86.5% probability of benefit in patients aged below 70 compared to 22% in those aged above 70; (ii) according to the time since symptoms onset (Pr Interact, 99%), with a 99.9% probability of a more than trivial benefit when lower than 7 days compared to a < 0.1% probability when delayed by 7 days or more; and (iii) according to use of remdesivir (Pr Interact, 91%), with a 90.1% probability of benefit in patients receiving remdesivir compared to 19.1% in those who did not.ConclusionsIn this exploratory post hoc Bayesian analysis, compared with standard-of-care DXM, high-dose DXM may benefit patients aged less than 70 years with severe ARF that occurred less than 7 days after symptoms onset. The use of remdesivir may also favour the benefit of DXM20. Further analysis is needed to confirm these findings.Trial registration: NCT04344730, date of registration April 14, 2020 (https://clinicaltrials.gov/ct2/show/NCT04344730?term=NCT04344730&draw=2&rank=1); EudraCT: 2020-001457-43 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-001457-43).

【 授权许可】

CC BY   
© La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF) 2023

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