The group of Philippe Gautret (IHU-Méditerranée Infection, Marseille, France) presented their results on a non-randomized clinical trial using two antibacterial agents – hydroxychloroquine and azithromycin – for the treatment of COVID-19.
The results are promising, but the number of patients enrolled is small, and the study is not a randomized clinical trial. Also, 6 of 26 patients in the treatment group were lost to follow-up, and no intention treat analysis has been included yet in the initial report.
The idea to use hydroxychloroquine, was based on a trial conducted in Chinese patients with COVID19 which showed a significant effect of chloroquine (an old antimalarial drug) on viral clearance as well as clinical outcome. The dosing regimen for chloroquine was 500mg twice a day for ten days.
Hydroxychloroquine, which is an analogue of chloroquine, has been demonstrated to have anti-SARS-CoV activity in vitro, and has a better safety profile than chloroquine.
Azithromycin has been showed to be active in vitro against Zika and Ebola viruses, and prevent severe respiratory tract infections when given to patients with viral infection.
This study enrolled hospitalized patients older than 12 years old with documented SARS-CoV-2 carriage in nasopharyngeal sample on admission. Patients with allergy or known contraindications to the drug (s.a. retinopathy, G6PD deficiency, QT prolongation) were excluded, as well as pregnant or breastfeeding patients.
The primary endpoint was virological clearance on day 6.
The treatment regimen is hydroxychloroquine sulfate PO 200 mg TID x 10 days. The patients who refused treatment or were excluded based on criteria served as controls to the treatment group. Azithromycin was given to 6 patients (not part of the protocol) to prevent bacterial infection, at a dose of 500mg PO x 1 then 250mg/day x 4 days.
Results of preliminary data showed that 70% of treatment group were virologicaly cured at day 6, compared with 12.5% in the control group (p = 0.001). Subgroup analysis of patients who received both hydroxychloroquine and azithromycin showed that 100% of patients treated with both antibiotics were virologicaly cured, compared to 57.1% of patients treated with only hydroxychloroquine and 12.5% in the control group (p<0.001).
The study proposes that nasopharyngeal carriage of SARS-CoV2 can be cleared in 3-6 days in most patients. Of note, mean duration of viral shedding (based on data from COVID cases in China) was 20 days (and up to 37 days).
Figure below: percentage of patients with (+) nasopharyngeal samples through day 6.
Figure below: percentage of patients with (+) nasopharyngeal samples through day 6. Treatment group divided into 2 subgroups – hydroxychloroquine +/- azithromycin.
Raw data provided in the supplemental tables. I colorized the table to show clearly why the data seems promising, with the limitations as discussed above.
Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of
COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of
Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949