PMID: identifiant
de la référence Pubmed : |
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 (21072246)  |
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| titre : |
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Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial. |
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| auteur(s) : |
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Xavier Duval1, 2, Sylvie Van Der Werf3, 4, Thierry Blanchon5, Anne Mosnier6, Maude Bouscambert-Duchamp7, 8, Annick Tibi9, Vincent Enouf3, Cécile Charlois-Ou10, Corine Vincent1, 11, Laurent Andreoletti12, 13, Florence Tubach1, 11, Bruno Lina7, 8, France Mentré1, 11, Catherine Leport ( ) 10, 14, Bivir Study Group Collaboration(s) |
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| laboratoire : |
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| résumé : |
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BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo. METHODS AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008-2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, =192; O, n=176; Z, n=173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n=157), O (n=141), and Z (n=149) arms had RT-PCR<200 cgeq/µl (-13.0%, 95% confidence interval [CI] -23.1 to -2.9, p=0.025; +12.3%, 95% CI 2.39-22.2, p=0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p=0.060, p=0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0-4.0, p=0.018; +0.0, 95% CI -3.0 to 3.0, p=0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n=13; O, n=4; and Z, n=5 patients, respectively). CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.govNCT00799760. |
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| domaine : |
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Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1549-1277 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pmed.1000362 |
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| journal : |
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| Audience : |
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internationale |
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| date de publication : |
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2010 |
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date de publication
électronique : |
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02/11/2010 |
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| volume : |
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7 |
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| numéro : |
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11 |
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| page, identifiant, ... : |
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e1000362 |
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| Descripteur(s) MeSH : |
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Adult – Antiviral Agents – Double-Blind Method – Drug Therapy – Combination – Female – Humans – Influenza – Human – Male – Middle Aged – Oseltamivir – Treatment Outcome – Zanamivir |
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| contrat, financement : |
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This work was supported by a research grant from the French Ministry of Health. The sponsor was: Département à la Recherche Clinique et au Developpement, Assistance Publique à Hopitaux de Paris (Programme hospitalier de recherche clinique, AOM 06060 and AOM 08209). |
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