Safety and efficacy of favipiravir in COVID-19 patients with pneumonia. A randomized, double-blind, placebo-controlled study (FAVID)
Juan P Horcajada, Rebeca Aldonza, Mónica Real, Silvia Castañeda-Espinosa, Elena Sendra, Joan Gomez-Junyent, Inmaculada López-Montesinos, Silvia Gómez-Zorrilla, Silvia Briansó, Montserrat Duran-Taberna, Andrés Fernández, Cristina Tarragó, Teresa Auguet-Quintillá, Maria Arenas-Miras, Itziar Arrieta‐aldea, Esperanza Cañas-Ruano, Roberto Güerri‐fernandez, Hernando Knobel, Maria Milagro Montero, Ivan Pelegrín, Francisca Sánchez‐martínez, Luisa Sorlí, Judith Villar‐garcía, Ajla Alibalic, Javier Camaron, Anna Maria Febrer, Laia Bertran, Andrea Barrientos
Pneumonia, doi:10.1186/s41479-023-00124-6
Purpose To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia. Methods A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was "time to clinical improvement, " measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame.
Results Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group. Conclusions Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.
Authors' contributions Conceptualisation: JPH, TAQ, AF, RA and CT. Data collection: MR, SCE, ES, JGJ, ILM, SGZ, SB and MDT. Data quality: RA. Formal analyses: RA. Project administration: AF, RA and CT. Evidence synthesis: JPH, TAQ, RA and CT. Writing-original draft: JPH, TAQ, RA and CT. Funding acquisition: AF, RA and CT. Writing-review and editing: JPH, TAQ, RA and CT. All authors have read and agreed to the published version of the manuscript.
Declarations Ethics approval and consent to participate The competing Ethics Committee of Hospital del Mar, Barcelona, Spain, approved the study protocol on 31 st of July 2020.
Competing interests JPH has received consulting fees from Gilead, Menarini and TFF Pharmaceuticals, and participated in educational activities from MSD, Pfizer and Angelini. All other authors have no conflicts of interests.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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