Oral clarithromycin in COVID-19 of moderate severity: the ACHIEVE open-label trial using concurrent matched comparators

ABSTRACT

Background: To study the efficacy of oral clarithromycin in moderate COVID-19. Methods: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end-of-treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection; and as at least 50% decrease of the respiratory symptoms score the without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells, and safety were assessed. Results: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. Conclusions: Early clarithromycin treatment provides most of clinical improvement in moderate COVID-19 (Trial Registration ClinicalTrials.gov, NCT04398004)