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A Randomized Controlled Trial

Arnold S. Monto, MD; D. Paul Robinson, MD; M. Louise Herlocher, PhD; James M. Hinson, Jr, MD; Michael J. Elliott, MD; Adam Crisp, PhD

JAMA. 1999;282:31-35.

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.

Author Affiliations: School of Public Health, University of Michigan, Ann Arbor (Drs Monto and Herlocher); University of Missouri, Columbia (Drs Robinson and Hinson); Glaxo Wellcome Inc, Research Triangle Park, NC (Dr Elliot); and Glaxo Wellcome Inc, Greenford, England (Dr Crisp).

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