Context The neuraminidase inhibitor zanamivir, a sialic acid analog administered
directly to the respiratory tract, has been demonstrated in clinical studies
to be effective in treatment of type A and B influenza. It has also been shown
to prevent influenza infection and disease in an experimental model.
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] years)
were recruited in November 1997, before the influenza season.
Intervention At the start of the influenza outbreak, 554 subjects were randomized
to receive placebo and 553 to receive zanamivir. The drug, 10 mg once 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 isolation when symptoms
were reported within 3 days of illness onset. Infection was also identified
by testing paired serum samples for rise in antibody titer 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 the case definition and 84% efficacious (95% CI, 55%-94%; P=.001) in preventing laboratory-confirmed illnesses with
fever. All influenza infections occurring 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 adverse 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 tolerated
in the prevention of influenza for a 4-week period in healthy adults.