Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness
Authors: Gamiño-Arroyo Ana E , Guerrero M Lourdes , McCarthy Sean , Ramírez-Venegas Alejandra , Llamosas-Gallardo Beatriz , Galindo-Fraga Arturo , Moreno-Espinosa Sarbelio , Roldán-Aragón Yuri , Araujo-Meléndez Javier , Hunsberger Sally , Ibarra-González Violeta , Martínez-López Julia , García-Andrade Luis A , Kapushoc Heather , Holley H Preston , Smolskis Mary C , Ruiz-Palacios Guillermo M , Beigel John H ,   Mexico Emerging Infectious Diseases Clinical Research Network (LaRed), Guerrero M Lourdes , Gamiño-Arroyo Ana E , Ramírez-Venegas Alejandra , Bautista Nora , Nolasco-Reza Angélica , Llamosas-Gallardo Beatriz , Ortiz-Hernández Ana A , Andrade-Platas Diana , Estevez-Jimenez Juliana , Galindo-Fraga Arturo , Roa-Martínez Bricia , Cruz-Gaona Itzel , Aguilar-Cruz Diana , Moreno-Espinosa Sarbelio , González-Matus Mónica , Mendoza-Garcés Luis , Araujo-Meléndez Javier , Perea-Guzmán Norma , Sandoval-Gutiérrez Ana , Hernández-Ramírez Daniel , Hernández-Sánchez Pedro Gerardo , Roldán-Aragón Yuri A , Davila-Cruz Alejandra N , Ibarra-González Violeta , Martínez-López Julia , García-Andrade Luis A , Ruiz-Palacios Guillermo M , Beigel John H , Smolskis Mary , Hunsberger Sally , Sean McCarthy H , Grue Louis , Burge Gregory , Cox Roxanne , Holley Preston , Cristillo Anthony , Nahed Nasreen , López Wendolyne , Becerril-Ruiz Eli Xchel , Quidgley Peter , Arroyo-Figueroa Hugo 
Published: January 2019

Abstract

Background
Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness.

Methods
From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4–11 years and 1–3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection.

Results
Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0–9.0) days in the NTZ group vs 7.0 (IQR, 4.0–9.0) days in the placebo group (P = .56). Duration of hospitalization between the 2 treatments was similar in children (P = .29) and adults (P = .62), influenza A and B (P = .32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events.

Conclusions
Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ.

Clinical Trials Registration
NCT02057757.