Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness

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.

Keywords: hospitalized; influenza-like illness; nitazoxanide; respiratory virus.

Figure 1.

Trial profile. Abbreviations: ITT, intention-to-treat; NTZ, nitazoxanide; PCB, placebo; SOC, standard of care.

Figure 2.

Time to hospital discharge (intention-to-treat population) in adults and children with severe influenza-like illness. Adult population: nitazoxanide (NTZ) + standard of care (SOC) (n = 63): Kaplan-Meier estimate of the median (8.0 [interquartile range {IQR}, 6.0–11.0]) vs placebo + SOC (n = 63): Kaplan-Meier estimate of the median (8.0 [IQR, 6.0–10.0]); Fay-Shaw formulation of the rank-sum statistic, P = .62. Child population: NTZ + SOC (n = 67): Kaplan-Meier estimate of the median (5.0 [IQR, 3.0–7.0]) vs placebo + SOC (n = 64): Kaplan-Meier estimate of the median (5.0 [IQR, 4.0–8.0]); Fay-Shaw formulation of the rank-sum statistic, P = .30.