title: Inhaled zanamivir versus placebo for the prevention of influenza outbreaks in an unvaccinated long-term care population.
abstract: BACKGROUND
  Antiviral chemoprophylaxis effectiveness for influenza control has not been prospectively established for unvaccinated residents of long-term care facilities. This study evaluated the efficacy and tolerability of zanamivir against the standard of care (no intervention, ie, placebo) for influenza outbreak control in a largely unvaccinated institutionalized population.
  
  
  OBJECTIVE
  To evaluate the efficacy and tolerability of zanamivir versus placebo for influenza outbreak control in long-term care facilities.
  
  
  METHODS
  This double-blind, randomized, placebo-controlled study prospectively enrolled/followed residents of long-term care facilities (LTCF) at 12 centers for 1 to 3 influenza seasons (1997 to 2000). Following influenza outbreak declaration, asymptomatic subjects were randomized for prophylaxis to inhaled zanamivir 10 mg or inhaled placebo given once daily for 14 days. The proportion of randomized subjects who during prophylaxis developed symptomatic, laboratory-confirmed influenza (SLCI) was the primary end point.
  
  
  RESULTS
  Influenza outbreaks were explosive. The attack rates varied from 9.5 to 14.8 per 100 residents. Of 1763 consents given and resulting in 494 randomizations, 49% received zanamivir and 51% placebo; 66% were elderly and 9% were vaccinated. SLCI occurred in 6% of zanamivir and 9% of placebo subjects (P = .355; protective efficacy for zanamivir = 29%, 95% confidence interval 31% to 62%), and symptomatic influenza confirmed by culture in 2% and 6%, respectively (P = .052; protective efficacy = 65%, 95% confidence interval 8.5% to 86%). Zanamivir use was also associated with a 70% (95% confidence interval 13% to 89%) reduction in laboratory-confirmed influenza with fever (2% vs 6%, P = .043). Influenza B was not detected. Zanamivir was well tolerated. No virus isolate demonstrated zanamivir resistance.
  
  
  CONCLUSIONS
  The protective efficacy of zanamivir versus placebo for SLCI was marginal, for all laboratory confirmed illnesses, but significant against culture proven and febrile influenza, suggesting zanamivir can be effective for outbreak control and symptom reduction of unvaccinated institutionalized residents. Zanamivir had an acceptable safety profile in elderly, high-risk LTCF residents and was not associated with the emergence of resistant strains.
authors.affiliation: Vilnius University, Vilnius, Lithuania.
authors.forename: Arvydas
authors.initials: A
authors.lastname: Ambrozaitis
authors.forename: Stefan
authors.initials: S
authors.lastname: Gravenstein
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: van Essen
authors.forename: Ethan
authors.initials: E
authors.lastname: Rubinstein
authors.forename: Ligita
authors.initials: L
authors.lastname: Balciuniene
authors.forename: Ausra
authors.initials: A
authors.lastname: Stikleryte
authors.forename: Catriona
authors.initials: C
authors.lastname: Crawford
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
authors.forename: Peter
authors.initials: P
authors.lastname: Shult
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018890:Chemoprevention; D003428:Cross Infection / Q000517:prevention & control* / Q000821:virology; D004196:Disease Outbreaks / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009735:Nursing Homes; D010919:Placebos; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014611:Vaccination; D053243:Zanamivir / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D010919:Placebos; D053243:Zanamivir