A randomized, double-blind, placebo-controlled trial evaluating the safety of early oseltamivir treatment among children 0–9 years of age hospitalized with influenza in El Salvador and Panama

Oseltamivir reduces symptom duration among children with uncomplicated influenza, but few data exist on treatment efficacy and tolerability among hospitalized children, particularly among infants aged <1 year. We evaluated tolerability and efficacy of oseltamivir treatment of children aged 0–9 years hospitalized with influenza. We conducted a double-blind, randomized, placebo-controlled trial at tertiary care hospitals in El Salvador and Panama. Primary outcomes were length of hospitalization and increased work of breathing. Children were eligible if hospitalized <7 days after symptom onset with cough or sore throat plus tachypnea. Children were randomized 1:1 to receive oseltamivir or placebo; had swabs collected at enrollment for influenza RT-PCR testing; were assessed at enrollment and every 12 h for work of breathing; and were followed for adverse events through 7 days after discharge. Analyses were intention-to-treat. Overall, 683 children were randomized (oseltamivir, n = 341, placebo n = 342). Fifty-three percent were aged <1 year and 30 had influenza (oseltamivir, n = 19; placebo, n = 11). The study was terminated early after enrollment of 21% of the sample size due to lower than anticipated participant accrual. Using Kaplan-Meier analysis, there was no significant difference in median length of hospitalization (3 days, IQR 2–4 vs. 5 days, IQR 3–7, p = 0.22) and increased work of breathing (36 h, IQR 24–72 vs. 96 h, IQR 13–108, p = 0.14) between oseltamivir versus placebo recipients. There was no difference in adverse events between groups. Oseltamivir treatment was well tolerated among hospitalized children, including among infants aged <1 year.