Fujita Health University announced the main findings from the multicenter, open-label, randomized clinical trial to evaluate the effect of favipiravir on the viral load reduction among asymptomatic and mildly ill patients with SARS-CoV-2 infection. The trial was carried out in 47 medical institutions nationwide, conducted by Fujita Medical University Hospital as the representative institution (Principal Investigator: Dr. Yohei Doi, Department of Infectious Diseases, Fujita Health University Hospital).
A total of 89 patients with the coronavirus disease 2019 (COVID-19) participated in this study between early March 2020 and mid-May 2020. Among them, 44 were randomly assigned to the early treatment group (oral favipiravir starting on day 1) and 45 to the delayed treatment group (oral favipiravir starting on day 6). One subject in the delayed treatment group withdrew from the study immediately after randomization, leaving 44 clinically evaluable patients in each group. Virological evaluation was conducted among 69 subjects (36 patients in the early treatment group and 33 in the delayed treatment group) after excluding 19 patients with whom nasopharyngeal PCR was negative on day 1. No subject experienced progression of disease or death during the 28-day study participation.
The prespecified primary endpoint of cumulative viral clearance by day 6 (prior to initiation of oral favipiravir in the delayed treatment group) was met by 66.7% of subjects in the early treatment group and 56.1% of subjects in the delayed treatment group, with an adjusted hazard ratio of 1.42 (95% confidence interval = 0.76-2.62, P = 0.269).
A prespecified secondary endpoint of 50% reduction in the viral load, on the logarithmic scale by day 6, was met by 94.4% of subjects in the early treatment group and 78.8% of subjects in the delayed treatment group, with an adjusted odds ratio of 4.75 (95% confidence interval = 0.88-25.76, P = 0.071).
A prespecified exploratory endpoint of mean time to defervescence below 37.5°C was 2.1 days in the early treatment group and 3.2 days in the delayed treatment group, with an adjusted hazard ratio of 1.88 (95% confidence interval = 0.81-4.35, P = 0.141).
Adverse events related to administration of favipiravir included increase in blood uric acid levels (84.1%), blood triglyceride levels (11.0%), alanine aminotransferase levels (8.5%), and aspartate aminotransferase levels (4.9%). These were subclinical abnormal laboratory findings, and they resolved in most of the 38 subjects from whom repeat levels were available 5 days or more after completion of oral favipiravir. No subject developed gout.
The above findings suggested trends toward earlier viral clearance and defervescence in the early treatment group compared with the delayed treatment group, though the differences were not statistically significant. Regarding adverse events, reversible increase in uric acid levels was observed in most subjects while they received favipiravir, and no serious adverse events were noted otherwise. Full data of this study will be published as soon as possible.
This study was conducted as part of research grant “Study on multicenter open-label randomized clinical trial of favipiravir to evaluate the viral load reduction effect in asymptomatic and mildly ill patients with SARS-CoV2 infection/A multicenter observational study to evaluate the clinical course of moderate and severe patients receiving favipiravir” from the Japan Agency for Medical Research and Development (grant number: 19fk0108150s0001) to Fujita Health University.