GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia

Abstract

Background. We aimed to determine whether a 6-day course of intravenous methylprednisolone (MP) improves outcome in patients with SARS CoV-2 infection at risk of developing Acute Respiratory Distress Syndrome (ARDS). Methods. Multicentric, partially randomized, preference, open-label trial, including adults with COVID-19 pneumonia, impaired gas exchange and biochemical evidence of hyper-inflammation. Patients were assigned to standard of care (SOC), or SOC plus intravenous MP [40mg/12h 3 days, then 20mg/12h 3 days]. The primary endpoint was a composite of death, admission to the intensive care unit (ICU) or requirement of non-invasive ventilation (NIV). Results. We analyzed 85 patients (34, randomized to MP; 22, assigned to MP by clinician preference; 29, control group). Patient age (mean 68±yr) was related to outcome. The use of MP was associated with a reduced risk of the composite endpoint in the intention-to-treat, age-stratified analysis (combined risk ratio -RR- 0.55 [95% CI 0.33-0.91]; p=0.024). In the per-protocol analysis, RR was 0.11 (0.01-0.83) in patients aged 72 yr or less, 0.61 (0.32-1.17) in those over 72 yr, and 0.37 (0.19-0.74, p=0.0037) in the whole group after age-adjustment by stratification. The decrease in C-reactive protein levels was more pronounced in the MP group (p=0.0003). Hyperglycemia was more frequent in the MP group. Conclusions A short course of MP had a beneficial effect on the clinical outcome of severe COVID-19 pneumonia, decreasing the risk of the composite end point of admission to ICU, NIV or death.

Drug treatments for covid-19: living systematic review and network meta-analysis

“…After screening 7285 titles and abstracts and 122 full texts, 32 unique randomised controlled trials were identified that evaluated drug treatments as of 20 July 2020 (fig 1). 30313233343536373839404142434445464748495051 Searches of living evidence retrieval services identified one additional eligible randomised controlled trial 52. Eighteen randomised controlled trials have been published in peer reviewed journals, and 14 only as preprints.…”

“…Of the 32 included drug trials, six evaluated treatment against active comparators, 18 evaluated treatment against standard care or placebo, and two evaluated different durations or doses of the same treatment. Our analyses were performed on 26 June 2020 and include 20 randomised controlled trials 3134353637383941424344454647484950Table 1. presents the characteristics of the included studies.…”

“…No other discrepancies between the reporting of our outcomes of interest in trial reports and protocols or registrations were noted. One trial did not report outcomes in the groups as randomised; the authors shared outcome data with us in the groups as randomised 49…”

“…All analyses reached convergence based on trace plots and a Brooks-Gelman-Rubin statistic less than 1.05. Two randomised controlled trials that studied glucocorticoids differed substantially in size (the Randomised Evaluation of COVID-19 therapy (RECOVERY) trial enrolled 6425 patients48 and GLUCOCOVID 6349), thus we performed a fixed effects analysis for the direct pairwise analysis for the outcomes that were reported in both of the trials (mortality and mechanical ventilation). This analysis was separate from the network meta-analyses, which was conducted with random effects.…”

SARS-CoV-2 organising pneumonia: ‘Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?’

“… 26 These results are consistent with and add validation to multiple recently published randomised and cohort studies from Italy, Spain and the USA showing an association of corticosteroid treatment with decreased mortality and need for ventilators. 27–29 …”