Azithromycin and doxycycline of no benefit to COVID-19 patients, finds analysis

Trial finds neither azithromycin nor doxycycline meaningfully improve recovery times or reduce risk of hospitalisation in non-hospitalised COVID-19 patients.

green coronavirus particle punching a medicine capsule (red and white) - idea of coronavirus not affected by antibiotics

Preliminary trial data suggests that the commonly used antibiotics, azithromycin and doxycycline, do not reduce recovery time for COVID-19 patients aged 50 years plus in the community.

The UK’s ‘Platform Randomised trial of INterventions against COVID-19 In older people’ (PRINCIPLE) trial released preliminary results to provide real-time information in the pandemic. Full results will be made available as a peer-reviewed publication once follow-up and analysis has been completed for all participants.

Azithromycin and doxycycline were investigated as separate treatments in the trial to see if they might be suitable for use in the community to help people recover more quickly and prevent the need for hospital admission. Both antibiotics are currently being used by some doctors in the hope of treating COVID-19 in the early stages of the illness.

No beneficial effect in patients over 50

The interim analyses show that neither treatment reduces the time taken for people aged over 50 to first report that they feel recovered sufficiently to achieve meaningful clinical benefit. Therefore, no further people are therefore being randomised to receive azithromycin or doxycycline in the PRINCIPLE trial.

A total of 526 eligible participants were randomised to receive azithromycin (500 mg once daily for 3 days) within the first 14-days of onset of COVID-19 and compared with 862 participants randomised to usual care. After 28-days of follow-up, the results showed the estimated median time to self-reported recovery for azithromycin was 0.94 days shorter compared to usual care, with a low probability of being a meaningful benefit. There was also no evidence that azithromycin reduced hospitalisations or deaths compared with usual care.

Meanwhile, a total of 798 eligible participants were randomised to recieve doxycycline (200 mg on the first day followed by 100 mg a day for 6 days) within the first 14-days of onset of COVID-19 and compared with 994 participants randomised to usual care. Based on the interim incomplete data, both the estimated clinical benefit in the time to recovery (less than one day benefit) and hospitalisation rate (less than two percent benefit) is small for doxycycline. Final results for the doxycycline arm of the PRINCIPLE trial will be published after the full 28-day follow-up on all randomised participants are available. 

Professor Chris Butler from the University of Oxford’s Nuffield Department of Primary Care Health Sciences and Co-Lead of the PRINCIPLE trial, said: “Azithromycin and doxycycline have anti-inflammatory, anti-bacterial and possibly anti-viral effects and so were considered as potential treatments for COVID-19 in the community.

“While we are completing the analysis of the full range of study outcomes, and in different patient groups, our findings show that a three-day course of azithromycin or a seven-day course of doxycycline has no important clinical benefit in terms of the time taken to feeling recovered, and so will not help most patients with COVID-19 in the early stages their illness.

“These are two important findings, as both azithromycin and doxycycline have been used for treating COVID-19 in the community even in the absence of suspected bacterial pneumonia, so this practice should now be re-considered – particularly because overuse of antibiotics in the community can fuel the emergence of antimicrobial resistance.”

Professor Richard Hobbs, from the University of Oxford and co-lead of the PRINCIPLE trial, added: “This finding shows the importance of doing rigorous clinical trials in real-world settings before treatments are rolled out on a wide scale. Widespread use of treatment should not be based on laboratory studies and opinion alone.”

Recruitment into the budesonide arm of the PRINCIPLE trial is continuing.

The PRINCIPLE trial did not assess whether azithromycin or doxycycline could help patients already admitted to hospitalisation; however, in December 2020 it was reported that the UK’s RECOVERY trial found no benefit to hospitalised patients from azithromycin.

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