Tags

Type your tag names separated by a space and hit enter

Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments.

Abstract

OBJECTIVES

To describe the potential benefits and harms of zanamivir.

DESIGN

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

Randomised placebo controlled trials in adults and children who had confirmed or suspected exposure to natural influenza.

MAIN OUTCOME MEASURES

Time to first alleviation of symptoms, influenza outcomes and complications, admissions to hospital, and adverse events in the intention to treat (ITT) population.

RESULTS

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.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

    , , , ,

    Source

    BMJ (Clinical research ed.) 348: 2014 Apr 09 pg g2547

    MeSH

    Adult
    Antiviral Agents
    Child
    Humans
    Influenza, Human
    Randomized Controlled Trials as Topic
    Treatment Outcome
    Zanamivir

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review
    Systematic Review

    Language

    eng

    PubMed ID

    24811412

    Citation

    Heneghan, Carl J., et al. "Zanamivir for Influenza in Adults and Children: Systematic Review of Clinical Study Reports and Summary of Regulatory Comments." BMJ (Clinical Research Ed.), vol. 348, 2014, pp. g2547.
    Heneghan CJ, Onakpoya I, Thompson M, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2547.
    Heneghan, C. J., Onakpoya, I., Thompson, M., Spencer, E. A., Jones, M., & Jefferson, T. (2014). Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ (Clinical Research Ed.), 348, pp. g2547. doi:10.1136/bmj.g2547.
    Heneghan CJ, et al. Zanamivir for Influenza in Adults and Children: Systematic Review of Clinical Study Reports and Summary of Regulatory Comments. BMJ. 2014 Apr 9;348:g2547. PubMed PMID: 24811412.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. AU - Heneghan,Carl J, AU - Onakpoya,Igho, AU - Thompson,Matthew, AU - Spencer,Elizabeth A, AU - Jones,Mark, AU - Jefferson,Tom, Y1 - 2014/04/09/ PY - 2014/5/10/entrez PY - 2014/5/9/pubmed PY - 2014/6/19/medline SP - g2547 EP - g2547 JF - BMJ (Clinical research ed.) JO - BMJ VL - 348 N2 - OBJECTIVES: To describe the potential benefits and harms of zanamivir. DESIGN: 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: Randomised placebo controlled trials in adults and children who had confirmed or suspected exposure to natural influenza. MAIN OUTCOME MEASURES: Time to first alleviation of symptoms, influenza outcomes and complications, admissions to hospital, and adverse events in the intention to treat (ITT) population. RESULTS: 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/24811412/Zanamivir_for_influenza_in_adults_and_children:_systematic_review_of_clinical_study_reports_and_summary_of_regulatory_comments_ L2 - http://www.bmj.com/cgi/pmidlookup?view=long&amp;pmid=24811412 DB - PRIME DP - Unbound Medicine ER -