Trials ‘provide definitive data’ that corticosteroids successful in treating COVID-19
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The use of corticosteroids improved the odds that adults who are critically ill with COVID-19 would survive, according to data from four studies recently published in JAMA.
“This is, in many respects, the single clearest answer we’ve had so far on how to manage terribly ill COVID-19 patients,” Derek Angus, MD, MPH, chair of the critical care medicine department at the University of Pittsburgh and investigator with Randomized Embedded Multifactorial Adaptive Platform-Community Acquired Pneumonia (REMAP-CAP), said in a press release.
WHO is updating its treatment recommendations for COVID-19 as a result of the findings, according to the release.
In the REMAP-CAP study, investigators analyzed patients from 121 sites in eight different countries who had received either a fixed 7-day course of 50 mg or 100 mg of hydrocortisone intravenously every 6 hours (n = 137); a shock-dependent course of 50 mg every 6 hours when shock was “clinically evident” (n = 146); or no hydrocortisone (n = 101). The investigators found that the 7-day fixed-dose course and shock-dependent dose of hydrocortisone both had high probabilities of benefit (93% and 80%, respectively) with regard to odds of being “alive and free of ICU-based respiratory or cardiovascular support within 21 days” vs. patients who did not receive hydrocortisone.
In the second study, the Community-Acquired Pneumonia: Evaluation of Corticosteroids, or CAPE COD, group in France randomly assigned an initial hydrocortisone dose of 200 mg daily that was lowered to 100 mg daily then 50 mg daily over a maximum of 14 days (n = 76) or placebo (n= 73) to patients who were admitted to the ICU for COVID-19-related respiratory failure. The investigators reported no significant difference in the rate of either death or “persistent respiratory support with mechanical ventilation or high-flow oxygen therapy” on day 21 between the two groups (42.1% and 50.7%, respectively). However, the group heeded a safety and data committee’s recommendation to stop the study early in light of results from the RECOVERY trial — which showed low-dose dexamethasone reduced the risk for death by one-third in ventilated patients with COVID-19 — thus causing “likely underpowered results.”
In the third study, investigators working on behalf of COALITION COVID-19 Brazil III randomly assigned patients with COVID-19 and moderate or severe acute respiratory distress syndrome to receive corticosteroids (n = 148) or corticosteroids and a starting dose 20 mg of IV dexamethasone daily (n = 151). The latter group’s dose was reduced to 10 mg daily if the patient was still in the ICU after 5 days. During the first 28 days of treatment, investigators found the corticosteroids-only cohort had 4 ventilator-free days (95% CI, 2.9-5.4) and the dexamethasone cohort had a mean of 6.6 ventilator-free days (95% CI, 5-8.2 days).
In the final study, the WHO Rapid Evidence Appraisal for COVID-19 Therapies, or REACT, Working Group conducted a prospective meta-analysis of seven randomized clinical trials that assessed the effectiveness of systemic dexamethasone, hydrocortisone or methylprednisolone (n = 678) vs. usual care or placebo (n = 1,025) in critically ill patients. The group identified fewer deaths among patients who received corticosteroids compared with those who received usual care or placebo (222 vs. 425 deaths; summary OR = 0.66; 95% CI, 0.53-0.82).
In a related editorial, Hallie C. Prescott, MD, MSc, an assistant professor at the University of Michigan’s School of Medicine, and Todd W. Rice, MD, MSc, an associate professor at Vanderbilt University Medical Center, applauded the collaborative effort but added that “many clinically important questions remain,” including the benefit of combining corticosteroids with remdesivir (Gilead).
“The consistent findings of benefit in these studies provide definitive data that corticosteroids should be first-line treatment for critically ill patients with COVID-19,” Prescott and Rice wrote.
References:
- Angus DC, et al. JAMA. 2020;doi:10.1001/jama.2020.17022.
- Dequin PF, et al. JAMA. 2020; doi:10.1001/jama.2020.16761.
- Prescott HC, Rice TW. JAMA. 2020;doi:10.1001/jama.2020.16747.
- Sterne JAC, et al. JAMA, 2020;doi:10.1001/jama.2020.17023.
- Tomazini BM, et al. JAMA. 2020;doi:10.1001/jama.2020.17021.