Randomised Trial of Efficacy and Safety of Inhaled Zanamivir in Treatment of Influenza A and B Virus Infections. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group

Lancet. 1998 Dec 12;352(9144):1877-81.

Abstract

Background: Influenza affects many people worldwide each year and has many troublesome symptoms. We investigated the efficacy and safety of the inhaled antiviral agent zanamivir as a treatment for influenza A and B infection.

Methods: In a randomised, double-blind, placebo-controlled trial, we recruited 455 patients aged 12 years and older with influenza-like symptoms of 36 h duration or less who lived in Australia, New Zealand, and South Africa. Eligible patients were randomly assigned 10 mg inhaled zanamivir (n=227) or placebo (n=228) twice daily for 5 days. All patients recorded symptoms on diary cards four times daily during treatment and twice daily for 9 days after treatment. We analysed all patients by intention to treat, influenza-positivity, and high risk of developing complications.

Findings: Compared with placebo, zanamavir relieved influenza symptoms a median of 1.5 days earlier in the intention-to-treat (p=0.011) and influenza-positive (p=0.004) populations, and 2 days earlier in patients who were febrile at entry [corrected]. In high-risk patients treated with zanamivir, symptoms were alleviated a median of 2.5 days earlier (p=0.048), fewer had complications (p=0.004), and fewer used complication-associated antibiotics (p=0.025) compared with placebo. The adverse event profiles were similar for zanamivir and placebo.

Interpretation: Zanamivir was well-tolerated and effective in decreasing the duration and severity of symptoms. Complications were also decreased in high-risk patients but these findings need to be confirmed in future studies due to the limited number of patients [corrected].

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Double-Blind Method
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use
  • Guanidines
  • Humans
  • Influenza A virus*
  • Influenza B virus*
  • Influenza, Human / drug therapy*
  • Neuraminidase / antagonists & inhibitors*
  • Pyrans
  • Safety
  • Sialic Acids / administration & dosage*
  • Sialic Acids / adverse effects
  • Sialic Acids / therapeutic use
  • Treatment Outcome
  • Zanamivir

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Guanidines
  • Pyrans
  • Sialic Acids
  • Neuraminidase
  • Zanamivir