Other corticosteroids also help COVID-19

While the benefits of dexamethasone for the severe disease of COVID-19 have been replicated in a Brazilian randomized trial, a World Health Organization-sponsored patient-level meta-analysis of ongoing randomized trials revealed a global corticosteroid We concluded that it was a class effect.

Both datasets, along with two other multicenter randomized controlled trials of corticosteroids in critically ill patients with COVID-19 JAMA on Wednesday.

All three trials deregistered in June 2020 based in the UK Recovery trial Dexamethasone will reduce mortality in a press release, Published results There is a 36% reduction in ventilated patients and an 18% reduction in patients receiving supplemental oxygen.

Results of new dexamethasone

of CoDEX multi-center, open label test By definition in Berlin, 299 Brazilian patients with COVID-19 and moderate to severe acute respiratory distress syndrome (ARDS) were randomized for 20 days, dexamethasone 20 mg for 5 days, then 10 mg for 5 days, Or until the ICU is excreted over standard care, or for standard care only.

For the main results, dexamethasone increased survival and ventilator-free days in the first 28 days by an average of 6.6 to 4.0 between controls (P= 0.04), Luciano Azevedo, MD, PhD, and colleagues at Sirio-Libanes Hospital in Sao Paulo.

“This reduction could be due to cheap, safe and widely available interventions like dexamethasone that could increase ventilator-free days even slightly, reducing the risk of ventilatory complications and ICU stays in a pandemic situation. Is related to the burden on the healthcare system,” the group concluded.

Dexamethasone also reduced the acute prevalence of the disease, resulting in a lower mean organ failure assessment (SOFA) score on day 7 than usual care (6.1 vs 7.5, P= 0.004).

However, unlike the RECOVERY trial, CoDEX had no effect on 28-day all-cause mortality (56.3% vs. 61.5% (standard treatment only), HR 0.97, 95% CI 0.72-1.31).

In an accompanying editorial, Dr. Harry Prescott, MD, University of Michigan, Ann Arbor and Todd Rice, MD, Vanderbilt University, Nashville, TN, argued that the difference could be explained by an early discontinuation of the trial. We cannot properly assess the impact of steroids on mortality.”

Dexamethasone did not result in an increase in secondary infections (21.9% vs. 29.1% with standard treatment), and-a little need for insulin for glucose control (31.1% vs. 28.3%)-other serious adverse effects Reduction of event cases (3.3% vs 6.1%).

Hydrocortisone results

Two other inadequate studies released with CoDEX are REMAP-CAP And Cape Covid..

REMAP-CAP 384 confirmed or suspected COVID-19 patients randomized Respiratory or cardiovascular organ support ICU with a 7-day fixed course of IV hydrocortisone (50 mg every 6 hours), shock-dependent course (50 mg every 6 hours if clinically apparent) , Or without hydrocortisone.

Both fixed-dose and shock-dependent hydrocortisone regimens outperformed the primary endpoint without organ support, with 93% and 80% probabilities in the Bayesian model, both of which were statistically significant “According to definitive researchers,” because they did not meet the designated criteria.

CAPE COVID was the only double-blind trial, Randomized 149 patients in French ICU for COVID-19-related acute respiratory failure Continuous intravenous infusion of hydrocortisone 200 mg / d or saline placebo. Hydrocortisone was similar to placebo in terms of primary endpoint of day 21 death or persistent dependence on mechanical ventilation or high-flow oxygen therapy (42.1% vs. 50.7%, P= 0.29).

Meta-analysis of corticosteroids

All three studies, along with invasive mechanical ventilation from recovery and three additional randomized trials (DEXA-COVID 19, CAPE STEROID, and steroid-SARI), assessed the WHO rapid evidence of COVID-19 therapy. (REACT) Working Group In that meta-analysis..

“The clinical trial group agreed to share data even before accepting individual trial data for primary publication,” Prescott and Rice said.

The meta-analysis included a total of 1,703 critically ill patients with COVID-19 recruited through June 9, 2020, selected to limit the impact of RECOVERY outcomes. They were randomized to systemic dexamethasone, hydrocortisone, or methylprednisolone, or received regular care or placebo.

Overall, these drugs reduced the 28-day mortality rate by 34% relative to controls (fixed effect OR 0.66, 95% CI 0.53-0.82) with little discrepancy between study results , Dr. Jonathan Sterne of the University of Bristol, United Kingdom, and colleagues.

Mortality impacts were similar across drugs, with an odds ratio of 0.64 for dexamethasone, 0.69 for hydrocortisone, and 0.91 for methylprednisolone (one study of 47 patients and 26 deaths). based on).

These findings suggest that “benefits are a general class effect of glucocorticoids, not specific to certain corticosteroids,” the editors said.

A meta-analysis also suggested similar effects of low-dose and high-dose corticosteroid therapy, but “these estimates were inaccurate, but the dose issue was not clearly answered.” The editor said.

“A meta-analysis suggests that COVID-19 and corticosteroids in critically ill patients with shock may not be associated with improved mortality, but the results show that this is outside the protocol in the usual care group. They tend to be biased both by corticosteroid use and patient exclusion, and they are already receiving corticosteroids at screening,” they added.

“The exact threshold for prescribing corticosteroids for individual patients is still unknown,” the editor warns, but the Sterne group concluded. “These results from different clinical and geographical settings indicate that corticosteroid therapy is a standard treatment component of critically ill patients with COVID-19 in the absence of convincing contraindications.”