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Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.


ABSTRACT:

Importance

Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.

Objective

To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.

Design, setting, and participants

Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios.

Exposures

Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).

Main outcomes and measures

The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events.

Results

A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P?Conclusions and relevanceIn this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

SUBMITTER: WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group 

PROVIDER: S-EPMC7489434 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.

Sterne Jonathan A C JAC   Murthy Srinivas S   Diaz Janet V JV   Slutsky Arthur S AS   Villar Jesús J   Angus Derek C DC   Annane Djillali D   Azevedo Luciano Cesar Pontes LCP   Berwanger Otavio O   Cavalcanti Alexandre B AB   Dequin Pierre-Francois PF   Du Bin B   Emberson Jonathan J   Fisher David D   Giraudeau Bruno B   Gordon Anthony C AC   Granholm Anders A   Green Cameron C   Haynes Richard R   Heming Nicholas N   Higgins Julian P T JPT   Horby Peter P   Jüni Peter P   Landray Martin J MJ   Le Gouge Amelie A   Leclerc Marie M   Lim Wei Shen WS   Machado Flávia R FR   McArthur Colin C   Meziani Ferhat F   Møller Morten Hylander MH   Perner Anders A   Petersen Marie Warrer MW   Savovic Jelena J   Tomazini Bruno B   Veiga Viviane C VC   Webb Steve S   Marshall John C JC  

JAMA 20201001 13


<h4>Importance</h4>Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.<h4>Objective</h4>To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.<h4>Design, setting, and participants</h4>Prospective meta-analysis that pooled  ...[more]

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