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A Randomized Controlled Trial

John J. Treanor, MD; Frederick G. Hayden, MD; Peter S. Vrooman, MD; Rick Barbarash, PharmD; Robert Bettis, MD; Dennis Riff, MD; Sudeep Singh, MD; Nelson Kinnersley; Penelope Ward, MD; Roger G. Mills, MD; for the US Oral Neuraminidase Study Group

JAMA. 2000;283:1016-1024.

Context  Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza.

Objective  To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection.

Design  Randomized, placebo-controlled, double-blind study conducted January through March 1998.

Setting  Sixty primary care and university health centers throughout the United States.

Participants  A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38°C or more plus at least 1 respiratory symptom and 1 constitutional symptom.

Interventions  Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209).

Main Outcome Measures  Duration and severity of illness in individuals infected with influenza.

Results  Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P<.001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P<.001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P<.001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P.05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P<.001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P<.001).

Conclusions  Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.

Author Affiliations: University of Rochester, Rochester, NY (Dr Treanor); University of Virginia, Charlottesville (Dr Hayden); PW Clinical Research, Winston-Salem, NC (Dr Vrooman); Hill Top Research, St Louis, Mo (Dr Barbarash); Edmonds Family Medicine Clinic, Edmonds, Wash (Dr Bettis); Advanced Clinical Research Institute, Anaheim, Calif (Dr Riff); SARC Research Center, Fresno, Calif (Dr Singh); Roche Global Development, Welwyn, England (Mr Kinnersley and Dr Ward); and Gilead Sciences, Foster City, Calif (Dr Mills).

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