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Higher-dose corticosteroids increased the risk of death in patients with COVID-19 and hypoxia, and who were receiving either no oxygen or simple oxygen only, compared with usual care that included low-dose corticosteroids, an analysis of the randomized RECOVERY trial showed.

Among over 1,200 patients, 18% of those randomly assigned to higher-dose dexamethasone died within 28 days compared with 12% of those assigned to usual care (rate ratio [RR] 1.56, 95% CI 1.18-2.06, P=0.0020), reported Martin J. Landray, PhD, of the University of Oxford in England, and researchers in the RECOVERY Collaborative Group.

In addition, more patients in the higher-dose group required invasive mechanical ventilation or died -- a key secondary outcome -- compared with the usual care group (19.6% vs 13.1%; RR 1.50, 95% CI 1.16-1.94), according to a study published on the preprint server .

"This is evidence that pushing the dose is harmful for people on oxygen," Landray told MedPage Today. "When the study stopped early, we had a number of questions. Is this an underestimate of the harm? We might have not got how much more harmful, but it's harmful, so there's no role for this treatment, no evidence it's helpful in this group of patients."

However, Landray pointed out that a 6-mg dose of dexamethasone is "clearly beneficial," as shown in a .

Corticosteroids are only helpful at certain stages of disease, Landray noted. "Early in the disease, the virus is the issue, the immune system is your friend." If the lungs are working, there's not that much inflammatory damage, he explained, "so you don't need steroids."

But as disease progresses, steroids are helpful, he added. "When people need oxygen some of the lung is damaged, so take a 6-mg dose. By the time they get worse and need some sort of mechanical ventilation, then combined immunosuppression treatments might be more beneficial. Possibly putting up the dose of steroids, but we don't know for sure."

The researchers also reported that higher-dose dexamethasone was associated with an excess of pneumonia due to non-COVID infection compared with usual care (10% vs 6%) and an increase in hyperglycemia requiring increased insulin dose (22% vs 14%, respectively).

The RECOVERY trial is ongoing, with the researchers continuing to investigate the benefits of corticosteroids, including a higher dose in COVID patients with more severe illness, requiring invasive mechanical ventilation.

The ongoing trial includes patients "that appear similar to those we studied in COVID STEROID 2," Anders Perner, MD, PhD, of Rigshospitalet in Copenhagen, Denmark, told MedPage Today. Perner and co-authors previously studied the benefit of a 12-mg dose of dexamethasone compared with a 6-mg dose.

"Our study showed benefit in patients who are critically ill from COVID-19," he said. However, he and his team reported results in that were not statistically significant, noting that "the trial may have been underpowered to identify a significant difference."

For the current study, Landray and team included 1,272 patients hospitalized with COVID and hypoxia who required no oxygen (1%) or simple oxygen only (99%) from May 2021 to May 2022. Overall, 659 patients were randomized to dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner, and 613 were randomized to usual care, which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner.

Of the randomized patients, 59% were in Asia, 40% were in the U.K., and 1% were in Africa. Nineteen percent had diabetes mellitus. Mean age was 61, with those randomized to higher-dose corticosteroids on average 1.9 years younger than those in the usual care group, and 60-61% were men.

In May 2022, the independent Data Monitoring Committee recommended that recruitment of patients receiving no oxygen or simple oxygen be stopped due to safety concerns.

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