Efficacy and Safety of Inhaled Zanamivir in the Prevention of Influenza in Community-Dwelling, High-Risk Adult and Adolescent Subjects: A 28-day, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

• Published in: Clinical therapeutics 2007-08, Vol.29 (8), p.1579-1590
• Main Authors: LaForce, Craig, MD, Man, Choy Y., BSc, Henderson, Frederick W., MD, McElhaney, Janet E., MD, Hampel, Frank C., MD, Bettis, Robert, MD, Kudule, Laila, MD, Harris, Julia, MSc, Yates, Philip, PhD, Tisdale, Margaret, PhD, Webster, Alison, MD
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Clinical trials; Disease prevention; Double-Blind Method; Drug resistance; Europe; Female; high; Humans; Influenza; Influenza, Human - prevention & control; Influenza, Human - virology; Internal Medicine; Male; Medical Education; Middle Aged; neuraminidase inhibitor; North America; prevention; risk; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vaccines; Virology; Viruses; zanamivir; Zanamivir - administration & dosage; Zanamivir - adverse effects
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2007.08.023

Abstract Background: Influenza can cause significant morbidity and mortality in subjects at high risk for complications, including the elderly (age ≥65 years) and those with chronic respiratory, cardiovascular, or metabolic conditions. Effective prophylaxis can significantly reduce the disease burden in this population. Previous studies conducted primarily in non-high-risk subjects have reported the efficacy of inhaled zanamivir in preventing influenza. Objective: This study investigated the efficacy and safety of zanamivir in preventing influenza in community-dwelling adult and adolescent subjects at high risk for complications of influenza. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in community-dwelling subjects aged ≥12 years who were at high risk for developing complications of influenza, were able to use the Diskhaler device (Glaxo Group Limited, Research Triangle Park, North Carolina), and were able to take the first dose of study medication within 5 days of laboratory-confirmed local influenza activity. Eligible subjects were randomized to receive inhaled zanamivir 10 mg or placebo once daily for 28 days. The primary end point was the proportion of randomized subjects who developed symptomatic influenza during prophylaxis, as confirmed by culture and/or serology. All adverse events (AEs) occurring after the first dose of study medication were recorded. Results: The study enrolled 3363 subjects, of whom 58% were female and 93% were white; the mean age of participants was 60.4 years (range, 12-94 years), and 4% were adolescents. Significantly fewer zanamivirtreated subjects developed symptomatic, laboratory- confirmed influenza during prophylaxis compared with placebo recipients (4/1678 vs 23/1685, respectively), representing a relative risk (RR) of 0.17 (95% CI, 0.07-0.44; P < 0.001) and a protective efficacy of 83%. The incidence of complications was reduced in zanamivir-treated subjects compared with placebo recipients (1/1678 and 8/1685), representing an RR of 0.12 (95% CI, 0.02-0.73; P = 0.042) and a protective efficacy of 88%. The numbers of zanamivir recipients (151/1678 [9%]) and placebo recipients (169/1685 [ 10 % ] ) who developed symptomatic influenza-like illness regardless of laboratory confirmation did not differ significantly (RR = 0.86; 95% CI, 0.70-1.06), indicating that zanamivir was not effective in preventing influenza-like illness that was not caused by influenza infection.