Efficacy and Safety of the Oral Neuraminidase Inhibitor Oseltamivir in Treating Acute Influenza: A Randomized Controlled Trial. US Oral Neuraminidase Study Group

JAMA. 2000 Feb 23;283(8):1016-24. doi: 10.1001/jama.283.8.1016.

Abstract

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 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 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 < or = .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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / therapeutic use*
  • Acute Disease
  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Influenza, Human / complications
  • Influenza, Human / drug therapy*
  • Influenza, Human / physiopathology
  • Male
  • Middle Aged
  • Neuraminidase / antagonists & inhibitors*
  • Oseltamivir
  • Severity of Illness Index
  • Statistics, Nonparametric

Substances

  • Acetamides
  • Antiviral Agents
  • Enzyme Inhibitors
  • Oseltamivir
  • Neuraminidase