Post-exposure prophylaxis with favipiravir among household close contacts to confirmed COVID-19 cases: A cluster-randomized trial (PEPfavi)

BACKGROUND: Household transmission of SARS-CoV-2 remains a key driver of community spread, with secondary attack rates in Thai households reaching approximately 50 %. There is limited evidence supporting the efficacy of antiviral post-exposure prophylaxis (PEP) in this context. METHODS: The phase 2/3, open-label, (1:1) cluster-randomized controlled trial in Thailand, 168 household close contacts from 76 index cases were enrolled to receive either favipiravir-PEP (FPV-PEP) (1600-2000 mg/day for 7 days) or usual care. The efficacy of FPV-PEP was investigated in preventing SARS-CoV-2 infection after contact with index cases. RESULTS: The incidence of confirmed SARS-CoV-2 infection was lower in the FPV-PEP group than in the usual care group (7.32 % vs. 14.47 %), although the difference was not statistically significant. A trend toward fewer early positive rapid diagnostic test results on day 3 was observed in the FPV-PEP group. Symptom development was less frequent among FPV-PEP recipients, with fewer cases of fever, rhinorrhea, and myalgia. A significantly higher probability of remaining asymptomatic and delayed symptom onset was observed in the FPV-PEP group. No participants developed severe COVID-19 or required hospitalization. CONCLUSION: FPV-PEP was associated with a lower incidence of fever, rhinorrhea, and myalgia among household contacts. While a reduction in secondary transmission was observed, it did not reach statistical significance. Further large-scale studies are warranted to clarify its role in preventing household transmission.