Although favipiravir does not improve clinical outcomes in all patients hospitalized with COVID-19 infection, it may provide some clinical benefit among those younger than 60 years. These study results were published in The Lancet Respiratory Medicine.
Researchers in the United Kingdom, Brazil, and Mexico conducted a multicenter, open-label, randomized-controlled trial between May 2020 and May 2021 to assess the effects of favipiravir for the treatment of COVID-19 infection. Patients hospitalized with confirmed or suspected COVID-19 infection were enrolled in the study. The researchers randomly assigned patients in a 1:1 fashion to receive either oral favipiravir plus standard care (n=251) or standard care alone (n=248). The primary outcome was time between treatment allocation and recovery or hospital discharge. Outcomes were assessed using competing-risks survival regression via Fine-Gray proportional subdistribution hazards model. Poisson regression was used to compare the occurrence of adverse events (AEs) between the cohorts.
Among patients in the favipiravir plus standard care and standard care alone cohorts, 57% and 65% were men, the median age was 60 (IQR, 46-72) and 58 (IQR, 49-68) years, and 50% and 50% had reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 infection, respectively. Among all patients, cardiovascular- (n=245) and endocrine-related (n=158) comorbidities were the most common.
Overall, no significant differences in time to recovery were observed between the cohorts (hazard ratio [HR], 1.06; 95% CI, 0.89-1.27). A post-hoc analysis performed among patients younger than 60 years showed time to recovery was significantly shorter among those who received favipiravir plus standard care vs standard care alone (HR, 1.35; 95% CI, 1.06-1.72; P =.01). There also were no significant between-group differences in the rate of mortality for patients younger than 60 years and those 60 years and older.
Further analysis demonstrated a significantly increased benefit in mechanical-ventilation free survival among patients younger than 60 years who received favipiravir plus standard care vs standard care alone (HR, 0.34; 95% CI, 0.13-0.83; P =.02). However, treatment-associated differences in mechanical-ventilation free survival were not observed among patients aged 60 years and older.
Fisher exact testing showed a significant difference in the percentage of AEs reported among patients in the favipiravir vs standard care alone cohorts (39% vs 30%; P =.005). In regard to severe AEs, no significant between-group differences were observed. Gastrointestinal- and neurologic-related AEs were the most commonly reported. Of note, a significantly increased number of renal-related AEs were reported among patients who received favipiravir vs those who received standard care alone (P =.03).
Study limitations include the open-label design and the inclusion of patients without RT-PCR-confirmed COVID-19 infection. Additionally, there were more men and patients with diabetes included in the standard care alone cohort.
According to the researchers “The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted for the treatment of COVID-19.”
Shah PL, Orton CM, Grinsztejn B, et al; on behalf of the PIONEER trial group. Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care. The Lancet Respiratory Medicine. Published online December 14, 2022. doi:10.1016/s2213-2600(22)00412-x