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.

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].