Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials

Sterne, Jonathan A C; Dı́az, Janet; Villar, Jesús; Murthy, Srinivas; Slutsky, Arthur S.; Perner, Anders; Jüni, Peter; Angus, Derek C.; Annane, Djillali; Azevedo, Luciano César Pontes; Du, Bin; Dequin, Pierre‐François; Gordon, Anthony; Green, Cameron; Higgins, Julian P. T.; Horby, Peter; Landray, Martin J; Lapadula, Giuseppe; Gouge, Amélie Le; Leclerc, Marie; Savović, Jelena; Tomazini, Bruno Martins; Venkatesh, Balasubramanian; Webb, Steve; Marshall, John C.

doi:10.1186/s13063-020-04641-3

Cited by 39 publications

(48 citation statements)

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“…A total of 2018 articles were identified, and 37 records 4,5,10–44 were finally included after successive screening, including 32 guidelines 4,5,11,14–20,22,23,25–44 (86.5%) published in English language and five 10,12,13,21,24 (13.5%) in Chinese language (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…Of the 37 guidelines included, ten 4,14,20,30,32,37–41 (27.0%) were developed by international panels (Table 1). Nine 8,10‐13,15,21,24,34,44 of included guidelines were developed in China (24.3%), five 21,26,35,36,44 (13.5%) in the United States, two in Australia 38,42 (5.4%), two in Canada 22 43 (5.4%), two in South Korea 17,33 (5.4%), and one each in Germany, 25 India, 16 Italy, 19 Mexico, 31 North America (USA and Canada), 26 Poland, 29 and Spain 27 .…”

Section: Resultsmentioning

confidence: 99%

“…Twenty‐five 4,5,10–12,14–18,21,24,25,27,29–31,34–36,38–40,42,44 guidelines (67.6%) provided COVID‐19 diagnosis‐related recommendations, including seven guidelines 12,17,21,24,38,40,42 (18.9%) that contained only diagnostic recommendations. Computed tomography (CT), reverse transcription‐polymerase chain reaction (RT‐PCR), X‐rays, lung ultrasound, and routine blood tests were the most frequently recommended tests for COVID‐19 diagnosis (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Lung ultrasound and blood test were recommended in six guidelines 14–16,27,31,34 (16.2%). Three guidelines 14,16,31 suggested lung ultrasound used in screening and following up of COVID‐19. Three guidelines 15,27,34 suggested blood test as the routine test way.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 30 guidelines 4,5,10,11,13–16,18–20,22,23,25–37,39,41,43,44 (81.1%) addressed the treatment of COVID‐19. Treatment options included supportive care, antiviral therapy, glucocorticoid therapy, antibiotics, immunoglobulin, extracorporeal membrane oxygenation (ECMO), convalescent plasma, and psychotherapy (Table 3).…”

Section: Resultsmentioning

confidence: 99%

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Consistency of recommendations and methodological quality of guidelines for the diagnosis and treatment of COVID‐19

Luo

Liu

Ren

et al. 2021

J Evidence Based Medicine

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Objective Since the beginning of the COVID‐19 epidemic, a large number of guidelines on diagnosis and treatment of COVID‐19 have been developed, but the quality of those guidelines and the consistency of recommendations are unclear. The objective of this study is to evaluate the quality of the diagnosis and treatment guidelines on COVID‐19 and analyze the consistency of the recommendations of these guidelines. Methods We searched for guidelines on diagnosis and/or treatment of COVID‐19 through PubMed, CBM, CNKI, and WanFang Data, from January 1, 2020 to August 31, 2020. In addition, we also searched official websites of the US CDC, European CDC and WHO, and some guideline collection databases. We included diagnosis and/or treatment guidelines for COVID‐19, including rapid advice guidelines and interim guidelines. Two trained researchers independently extracted data and four trained researchers evaluated the quality of the guidelines using the AGREE II instruments. We extracted information on the basic characteristics of the guidelines, guideline development process, and the recommendations. We described the consistency of the direction of recommendations for treatment and diagnosis of COVID‐19 across the included guidelines. Results A total of 37 guidelines were included. Most included guidelines were assessed as low quality, with only one of the six domains of AGREE II (clarity of presentation) having a mean score above 50%. The mean scores of three domains (stakeholder involvement, the rigor of development and applicability) were all below 30%. The recommendations on diagnosis and treatment were to some extent consistent between the included guidelines. Computed tomography (CT), X‐rays, lung ultrasound, RT‐PCR, and routine blood tests were the most commonly recommended methods for COVID‐19 diagnosis. Thirty guidelines were on the treatment of COVID‐19. The recommended forms of treatment included supportive care, antiviral therapy, glucocorticoid therapy, antibiotics, immunoglobulin, extracorporeal membrane oxygenation (ECMO), convalescent plasma, and psychotherapy. Conclusions The methodological quality of currently available diagnosis and treatment guidelines for COVID‐19 is low. The diagnosis and treatment recommendations between the included guidelines are highly consistent. The main diagnostic methods for COVID‐19 are RT‐PCR and CT, with ultrasound as a potential diagnostic tool. As there is no effective treatment against COVID‐19 yet, supportive therapy is at the moment the most important treatment option.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Consistency of recommendations and methodological quality of guidelines for the diagnosis and treatment of COVID‐19

Luo

Liu

Ren

et al. 2021

J Evidence Based Medicine

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Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19

Dequin

Heming

Meziani

et al. 2020

JAMA

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425

470

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Gouge, MSc; for the CAPE COVID Trial Group and the CRICS-TriGGERSep Network IMPORTANCE Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. OBJECTIVE To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. INTERVENTIONS Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). MAIN OUTCOMES AND MEASURES The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; PaO 2 :FIO 2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. RESULTS The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions,-8.6% [95.48% CI,-24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. CONCLUSIONS AND RELEVANCE In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome.

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Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19

Sterne

Murthy

Dı́az

et al. 2020

JAMA

Self Cite

1,966

1,337

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The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group 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 PARTICIPANTSProspective 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 I 2 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 MEASURESThe 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 < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I 2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that repo...

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Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials

Cited by 39 publications

References 0 publications

Consistency of recommendations and methodological quality of guidelines for the diagnosis and treatment of COVID‐19

Consistency of recommendations and methodological quality of guidelines for the diagnosis and treatment of COVID‐19

Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19

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