Efficacy of clarithromycin on COVID-19 pneumonia without oxygen administration; protocol for multicenter, open-label, randomized-controlled, 3-armed parallel group comparison, exploratory trial (CAME COVID study)

Abstract IntroductionThe coronavirus disease 2019 (COVID-19) epidemic has been emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, no treatment strategy has been established for mild COVID-19 patients who do not require oxygen administration. The spread of SARS -CoV-2 has been mostly through patients with mild COVID-19; therefore, treating patients with mild COVID-19 is critical in society. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza infection. In this study, we aimed to evaluate the efficacy of clarithromycin in patients with mild COVID-19. Methods and analysisThis is a multicenter, open-label, randomized controlled, 3-armed parallel group comparison, exploratory trial. Subjects with mild COVID-19 pneumonia who did not require oxygen administration were enrolled and randomly assigned in a 1:1:1 ratio to Group A (administration of clarithromycin 800 mg/day), Group B (administration of clarithromycin 400 mg/day), or Group C (standard treatment without clarithromycin). The primary endpoint was the number of days required to improve clinical symptoms as measured by the severity score. Secondary endpoints included days to recover the body temperature, proportion of subjects with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers, and pneumonia infiltrations. Ethics and disseminationThe study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all participants. The results of this study will be reported as journal publications. RegistrationThis study was registered at the Japan Registry of Clinical Trials (registration number: jRCTs071210011). Strengths and limitations of this studyThis is the first randomized controlled trial to evaluate the efficacy of clarithromycin against COVID-19 pneumonia, especially in patients with mild COVID-19 pneumonia who do not require oxygen administration.To date, no treatment strategy has been established for mild COVID-19 pneumonia.The major limitations of this study are its exploratory nature and relatively small sample size.Another limitation is the open-label study design and generalizability because this study was conducted only in Japan with Japanese patients.