Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza - A randomized controlled trial

Context Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenz a. Objective To evaluate the efficacy and safety of oseltamivir in the treatme nt 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 Uni ted 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 t emperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. Interventions Individuals were randomized to 1 of 3 treatment groups with i dentical 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 infec ted with influenza. Results Two individuals withdrew before receiving medication and were exclu ded from further analyses, A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% wit h both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and o seltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared wit h placebo (median, 103.3 hours). Severity of illness was reduced by 38% (me dian score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseitamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir tr eatment reduced the duration of fever and oseltamivir recipients returned t o usual activities 2 to 3 days earlier than placebo recipients (P less than or equal to .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltam ivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illn ess 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 seve rity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectivel y, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea a nd vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% an d 3.4%; P < .001). Conclusions Our data suggest that oral oseltamivir treatment reduces the du ration and severity of acute influenza in healthy adults and may decrease t he incidence of secondary complications.