RESUMO
Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).
Assuntos
Amidas/administração & dosagem , Antivirais/administração & dosagem , Tratamento Farmacológico da COVID-19 , Pirazinas/administração & dosagem , SARS-CoV-2/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Amidas/efeitos adversos , Antivirais/efeitos adversos , Doenças Assintomáticas , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Hospitalização , Humanos , Hiperuricemia/induzido quimicamente , Hiperuricemia/diagnóstico , Hiperuricemia/fisiopatologia , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazinas/efeitos adversos , Distribuição Aleatória , SARS-CoV-2/patogenicidade , Prevenção Secundária/organização & administração , Índice de Gravidade de Doença , Tempo para o Tratamento/organização & administração , Resultado do TratamentoRESUMO
A 38-year-old man with renal cell carcinoma was referred to our hospital because of a productive cough. He had received radiotherapy for lung metastasis and been treated with axitinib. Bronchoscopy revealed necrosis in the bronchi of the right middle and lower lobes. Culture of the necrotic bronchial specimen revealed methicillin-resistant Staphylococcus aureus (MRSA). Although radiotherapy in combination with axitinib carries a risk of causing airway toxicity, MRSA necrotizing bronchitis has not been reported. Physicians should consider the possibility of infectious necrotizing bronchitis if irradiated patients show prolonged respiratory symptoms.