Zanamivir in the prevention of influenza among healthy adults - a randomized controlled trial

Context The neuraminidase inhibitor zanamivir, a sialic add analog administ ered directly to the respiratory tract, has been demonstrated in clinical s tudies to be effective in treatment of type A acid B influenza. It has also been shown to prevent influenza infection and disease in an experimental m odel. Objective To examine the efficacy of zanamivir, administered once daily, in the prevention of influenza infection and disease. Design Double-blind, randomized, placebo-controlled trial. Setting Two midwestern university communities. Participants A total of 1107 healthy adults (mean age [range], 29 [18-69] y ears) were recruited in November 1997, before the influenza season. Intervention At the start of the influenza outbreak, 554 subjects were rand omized to receive placebo and 553 to receive zanamivir, The drug, 10 mg onc e per day, or identical placebo was administered by oral inhalation for a 4 -week period. Main Outcome Measures Illness occurrence was recorded by participants daily and records were evaluated weekly. Specimens were collected for viral isol ation when symptoms were reported within 3 days of illness onset. Infection was also identified by testing paired serum samples for rise in antibody t iter against the circulating influenza viruses. Results Zanamivir was 67% efficacious (95% confidence interval [CI], 39%-83 %; P<.001) in preventing laboratory-confirmed clinical influenza meeting th e case definition and 84% efficacious (95% CI, 55%-94%; P = .001) in preven ting laboratory-confirmed illnesses with fever. All influenza infections oc curring during the season, with or without symptoms, were prevented with an efficacy of 31% (95% CI, 4%-50%; P = .03). The nature and incidence of adv erse events in the zanamivir group did not differ from placebo. Compliance with the once-daily dosage was high. Conclusions Zanamivir administered once daily is efficacious and well toler ated in the prevention of influenza for a 4-week period in healthy adults.