Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. doi:10.1016/j.ijantimicag.2020.105949
Review written by:
Bryan Wang, edited by Shawn Sun
Yellow - Moderate evidence towards reducing viral load in patients, but lacks clinical outcomes and is not rigorously controlled.
The trial enrolled 20 COVID-19+ patients in the experimental group and 16 COVID-19+ patients in the control group. In the experimental group, 6 patients received azithromycin in combination with hydroxychloroquine and 14 received hydroxychloroquine alone. Their primary endpoint was the proportion of subjects achieving virologic clearance of SARS-CoV2 (undetectable by nasopharyngeal swab) day 6 after treatment initiation.
They found that there was a significant difference in achievement of virologic clearance between all patients who received hydroxychloroquine and control patients assayed on each of days 3 through 6 after treatment initiation (p0.05), with those receiving azithromycin in conjunction having a more significant effect size.
In order of importance:
The first caveat is that speed of progression from PCR-positive to PCR-negative nasal swabs is not an indicator of disease progression or severity, so no conclusions can be drawn about whether or not this treatment would be effective in improving clinical outcomes, though the study does not aim to test this. .
Another important limitation is that 6 patients in the hydroxychloroquine group did not complete the study (due to death, ICU transfer, patient discontinuation) and were not included in the outcome analysis. This represents a large part of the enrolled treatment group and includes severe cases, which, by virtue of elimination from the outcome analysis, may have biased toward increased likelihood of significance.
Difference in age between the control group (37.3) and the experimental group (51.2) is large, so cannot rule out an age-related effect.
The primary endpoint was the detection of virus in nasopharyngeal swabs at day 6 post inclusion in the study. However, the time between onset of symptoms and inclusion was not normalized in the study, and patients with longer time between onset and inclusion are more likely to test negative as time progresses. For the control group, asymptomatic patients were included for which this time would not be determined.
This trial was not blinded or randomized.