RECOVERY: Steroid Benefit in Severe COVID-19 Holds Up

The sickest patients hospitalized with COVID-19 who received dexamethasone, the low-cost steroid, had a significantly lower incidence of death versus patients receiving usual care, preliminary results from the U.K.-based RECOVERY trial found.

Incidence of death was significantly lower for patients in the dexamethasone group who received mechanical ventilation versus those receiving usual care (29.3% vs 41.4%, RR 0.64, 95% CI 0.51-0.81) and those receiving supplemental oxygen without mechanical ventilation (23.3% vs 26.2%, RR 0.82, 95% CI 0.72-0.94), reported Martin Landray, PhD, of the University of Oxford, on behalf of the RECOVERY Collaborative Group, and colleagues.

However, there was no significant difference in the incidence of death between groups among those patients who did not receive respiratory support (17.8% vs 14.4%, RR 1.19, 95% CI 0.91-1.55), Landray’s group wrote in the New England Journal of Medicine.

Overall mortality at 28 days was significantly lower in the dexamethasone group versus usual care (22.9% vs 25.7%, RR 0.83, 95% CI 0.75-0.93, P<0.001), the researchers noted.

These are not new results, with the U.K.-based Randomised Evaluation of COVID-19 Therapy (RECOVERY) investigators releasing topline interim results via press release on June 16. Back in June, the investigators said they would be submitting their data for peer review.

Commenting on June’s topline results at a press conference for the International AIDS Society’s COVID-19 conference last week, National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci, MD, characterized the topline results as “quite impressive” for individuals on ventilators requiring oxygen.

“That is very important, because it goes along exactly with what we know about pathogenic mechanisms, mainly that early on, you really want to block the virus, but keep the immune system intact, and later on, when you have aberrant inflammation, you want to dampen it,” he said.

Fauci said that based on the topline results, dexamethasone was now being recommended by the NIH clinical guidelines group for COVID-19 patients who meet the particular criteria used in the study, because of the “diminution of mortality.”

“In many respects, it’s now becoming the standard of care for advanced patients on ventilators and/or requiring oxygen,” he added.

Fauci also authored an accompanying NEJM editorial with H. Clifford Lane, MD, also of the NIAID, writing that the new findings on dexamethasone provide “clarity to an area of therapeutic controversy and probably will result in many lives saved.”

Landray and colleagues examined data for patients hospitalized with COVID-19 at 176 National Health Service organizations across the U.K. Patients were eligible if they had confirmed or suspected COVID-19 infection. Originally confined to patients age 18 and older, the age limit was removed on May 9, and pregnant and breast feeding women were eligible. Primary outcome was all-cause mortality within 28 days after randomization.

Overall, 2,104 patients were randomized to receive intravenous dexamethasone (6 mg per day), while 4,321 received usual care. They were a mean age of about 66, and 36% were women or girls. Over half had at least one chronic comorbidity, with 27% having heart disease, 24% with diabetes, and 21% with chronic lung disease.

At randomization, 16% were receiving mechanical ventilation, 60% received oxygen only, and 24% received neither.

Nearly all patients in the dexamethasone group received at least one dose of the drug, and the median duration of treatment was 7 days. However, 8% of those in the usual care group did receive dexamethasone as part of their care. About a quarter of patients in each group received azithromycin during the follow-up period.

Landray and colleagues noted that in addition to benefit in the sickest patients, there was also a clear benefit among patients treated more than 7 days following symptom onset “when inflammatory lung damage is likely to be more common.”

The dexamethasone group also had a shorter median duration of hospitalization versus usual care (12 days vs 13 days) and a greater probability of being discharged alive at 28 days, with the greatest effects seen among patients receiving mechanical ventilation at randomization.

Lane and Fauci said this work proves that “rigorous clinical research” can be conducted during a pandemic, similar to the large randomized trial conducted during the 2019 Ebola outbreak in the Democratic Republic of the Congo. The PALM study found two effective therapies for Ebola in a much more conclusive way than smaller studies during the earlier Ebola outbreak in West Africa, the editorialists said.

“It is our responsibility in the global medical research community to rapidly design, implement and complete studies of the most promising therapeutic agents and vaccines against this disease,” Lane and Fauci wrote.