Current best evidence for clinical care (more info)
BACKGROUND: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.
METHODS: In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
FINDINGS: Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).
INTERPRETATION: In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.
FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
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During the pandemic when trying to find out which treatments can be successfully used, it is just as important to find out what doesn't work. This trial provides that information for hospitalized patients. Thankfully, there were no significant adverse effects found in the trial group, but we have seen multiple instances of the development of antibiotic resistance when these medications are used injudiciously. Now we have more evidence of where they should not be used.
Negative trial but addresses an important question and intervention.
This gives more evidence for stopping macrolide therapy when infection is not overt, and for not using macrolidea for anti-inflammatory pathways.
This trial seems big enough to be worth paying attention to.
Respiratory physicians, intensivists, general physicians, emergency doctors are all involved in care of patients with COVID-19. They will appreciate the information generated by this large trial of azithromycin vs standard care in hospitalised patients. It did not improve important outcomes. There will be some quibbling about methods and crossovers during the trial, but in the context of the pandemic, this trial is successful: We can be confident that routine use of azithromycin in hospitalised COVID-19 patients is not effective.