In patients hospitalized with COVID-19, there was no significant difference in 28-day all-cause mortality between patients receiving azithromycin vs patients receiving the usual standard of care, according to study results published in the Lancet.
The Randomized Evaluation of COVID-19 Therapy trial (RECOVERY; Clinicaltrials.gov Identifier: NCT04381936) was conducted at 176 hospitals in the United Kingdom. Between April 7 and November 27, 2020, 9433 patients were enrolled: 2582 patients in the azithromycin group, 5181 patients in the usual care group, and 1670 patients in the other available RECOVERY treatment groups. The azithromycin group received azithromycin 500 mg once daily by mouth, nasogastric tube, or intravenous injection for 10 days or until discharge, whichever is sooner. The primary outcome was 28-day all-cause mortality.
Investigators observed no significant difference in the primary outcome between patients who did and did not receive azithromycin (rate ratio [RR], 0.97; 95% CI, 0.87-1.07; P =.50). Similarly, there were no significant differences in secondary outcomes between patients who did and did not receive azithromycin, particularly in time to discharge from hospital (RR, 1.04; 95% CI, 0.98-1.10; P =.19) and number of patients who progressed to invasive mechanical ventilation or death among those not on invasive mechanical ventilation at randomization (RR, 0.95; 95% CI, 0.87-1.03; P =.24).
Investigators reported 1 serious adverse reaction of pseudomembranous colitis related to azithromycin which the patient recovered with standard treatment.
Previous randomized controlled trials assessing the efficacy of azithromycin in COVID-19 hospitalized patients observed similar findings. In those 3 trials combined, there were 1223 patients and 130 deaths. Comparatively, the RECOVERY trial assessing azithromycin efficacy had 7763 patients and 1723 deaths, indicating sufficient power to detect modest treatment benefits.
Since study initiation, several treatment groups, including the azithromycin group, have been stopped, though the RECOVERY trial continues studying other therapeutic options.
Limitations of this study include lack of data regarding viral load laboratory markers, inflammatory status, immune response, coexistent bacterial infection, use of non-macrolide antibiotics, and radiological or physiological outcomes. Randomization was open-label to both participants and local hospital staff.
“Our results showed that the addition of azithromycin to routine clinical care of patients admitted to hospital with COVID-19 confers no clinical benefit, whether that be anti-inflammatory or antimicrobial,” the researchers concluded. Considering these results, widespread macrolide use in COVID-19 patients should be questioned as it can bring about a societal risk of harm by increasing the potential of resistance.
RECOVERY Collaborative Group. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. Published online February 2, 2021. doi:10.1016/S0140-6736(21)00149-5.