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UK Study Finds Antibiotics Azithromycin and Doxycycline Ineffective Against COVID-19

The UK-based PRINCIPLE study has found that the commonly-used antibiotics azithromycin and doxycycline are not generally effective in certain patients with early COVID-19.

The study evaluated each antibiotic as separate treatments in the trial – although interim data has found that neither drug reduced the time to self-reported recovery in patients aged over 50 years.

For the 526 patients randomised to receive azithromycin, the estimated median time to self-reported recover was 0.94 days shorter compared to standard care after 28 days of follow-up.

There was also no evidence that azithromycin reduced COVID-19-associated hospitalisations or death compared with standard care.

In the doxycycline arm, a total of 798 eligible participants were randomised to receive the antibiotic within the first 14 days of onset of COVID-19.

However, randomisation into this arm was stopped after it was deemed that there was a small probability that the drug would demonstrate a clinically meaningful benefit compared to standard care.

Based on the interim incomplete data, investigators found that both the estimated clinical benefit in the recovery time and hospitalisation rate was 'small' for doxycycline – less than a one-day benefit and less than 2% benefit, respectively.

In England, clinical guidance currently recommends treatment with oral doxycycline for suspected pneumonia in COVID-19 patients in the community – either if the cause is bacterial or if the cause is unclear and symptoms are particularly concerning.

Doctors across the country had been using the drugs to target COVID-19 when it is in its early stages.

“The PRINCIPLE trial shows that doxycycline is not effective as a treatment for suspected COVID-19 in the absence of bacterial pneumonia, and should not be used in this way,” the chief investigators of the study said in a statement.

"While I fully understand why colleagues would want to do everything for patients who might have COVID-19, PRINCIPLE usefully provides evidence that prescribing these antibiotics for most people with possible COVID-19 is not helpful,” said Simon de Lusignan, director of RCGP RSC and co-principal investigator of the PRINCIPLE trial.

Earlier this month, a study led by Imperial College London, known as REMAP-CAP, found that Roche's Actemra (tocilizumab) and Sanofi's Kevzara (sarilumab) cut the risk of death in critically ill COVID-19 patients.

This trial found that both Actemra and Kevzara reduced mortality by 8.6%, and also improved recovery times among patients who are critically ill with COVID-19.

This reflects a reduction in the relative risk of death by 24% when given to patients within 24 hours of entering intensive care.

On average, patients treated with these drugs were able to leave the ICU around a week earlier than those not receiving these treatments.

Useful Links: 

http://www.isrctn.com/ISRCTN86534580

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001209-22/GB