Systematic review of clinical study reports of randomised placebo controlled trials and regulatory information
DATA SOURCES: Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included 28 trials in stage 1 (judgment of appropriate study design) and 26 in stage 2 (formal analysis). For treatment of adults,
zanamivir reduced the time to first alleviation of symptoms of
influenza-like illness by 0.60 days (95% confidence interval 0.39 to 0.81, P<0.001, I(2)=9%), which equates to an average 14.4 hours' reduction, or
a 10% reduction in mean duration of symptoms from 6.6 days to 6.0 days. Time to first alleviation of symptoms was shorter in all participants when any relief drugs were allowed compared with no use.
Zanamivir did not reduce the risk of self reported investigator mediated
pneumonia (risk difference 0.17%, -0.73% to 0.70%) or radiologically confirmed
pneumonia (-0.06%, -6.56% to 2.11%) in adults. The effect on
pneumonia in children was also not significant (0.56%, -1.64% to 1.04%). There was no significant effect on
otitis media or
sinusitis in both adults and children, with only a small effect noted for
bronchitis in adults (1.80%, 0.65% to 2.80%), but not in children. There were no data to assess effects on admissions in adults and children.
Zanamivir tended to be well tolerated. In
zanamivir prophylaxis studies, symptomatic
influenza in individuals was significantly reduced (1.98%, (0.98% to 2.54%); reducing event rates from 3.26% to 1.27%, which means 51 people need to be treated to prevent one
influenza case (95% confidence interval, 40 to 103). In contrast, the prophylaxis effect on asymptomatic
influenza cases was not significant in individuals (risk difference 0.14%, -1.10% to 1.10%) or in households (1.32%, -2.20% to 3.84%). In households treated prophylactically there was an effect on symptomatic
influenza (14.84%, 12.18% to 16.55%), but this was based on only two small studies including 824 participants. Prophylaxis in adults reduced unverified
pneumonia (0.32%, 0.09% to 0.41%; NNTB (number needed to treat to benefit) 311, 244 to 1086) but had no effect on
pneumonia in children or on
bronchitis or
sinusitis in adults or children (risk difference 0.32%, 0.09% to 0.41%; NNTB 311, 244 to 1086).
CONCLUSIONS: Based on a full assessment of all trials conducted,
zanamivir reduces the time to symptomatic improvement in adults (but not in children) with
influenza-like illness by just over half a day, although this effect might be attenuated by symptom relief medication.
Zanamivir also reduces the proportion of patients with laboratory confirmed symptomatic
influenza. We found no evidence that
zanamivir reduces the risk of complications of
influenza, particularly
pneumonia, or the risk of hospital admission or death. Its harmful effects were minor (except for
bronchospasm), perhaps because of low bioavailability.