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BMJ Open. 2017 Jul 10;7(7):e014546. doi: 10.1136/bmjopen-2016-014546.

Factors associated with non-persistence to oral and inhaled antiviral therapies for seasonal influenza: a secondary analysis of a double-blind, multicentre, randomised clinical trial.

Author information

IAME (Infection, Antimicrobien, Modélisation, Evolution), UMR-1137, Inserm, Université Paris Diderot, Sorbonne Paris Cite, Paris, France.
Service de Biostatistique et Information Médicale, ECSTRA Team, UMR-1153, Inserm, Université Paris Diderot, Sorbonne Paris Cité, Hôpital Saint Louis, Paris, France.
Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille, France., Marseille, France.
ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d'Azur, Marseille, France., Marseille, France.
Faculte de Pharmacie, Université Paris Descartes, Paris, France.
Faculté de Médecine, Inserm Université Pierre et Marie Curie, U1136 - Institut Pierre Louis d'épidémiologie et de santé publique (IPLESP), Paris, France.
Institut Pasteur, Centre National de Référence des virus influenzae (Région-Nord), Unité de Génétique Moléculaire des Virus à ARN, Paris, France.
Réseau des Groupes Régionaux d'Observation de la Grippe (GROG), Coordination Nationale, Paris, France.
Faculté de Médecine Lyon Est, VirPatH, EA 4610, Université Claude Bernard Lyon 1, Lyon, France.
Laboratoire de Virologie & CNR des virus influenzae (site Lyon), Hospices Civils de Lyon, Lyon, France.



We aimed to evaluate and compare non-adherence to oral and inhaled antiviral therapies prescribed of a randomised clinical trial in outpatients with influenza A infection.


A parallel, three-arm, double-blinded trial randomly allocated antiviral therapies twice daily for 5 days: (1) oral oseltamivir plus inhaled zanamivir (arm OZ); (2) oseltamivir plus inhaled placebo (arm Opz); or (3) oral placebo plus inhaled zanamivir (arm poZ). Analysis of non-adherence was a secondary objective of the trial.


Outpatients were enrolled by 145 general practitioners throughout France during the 2008-2009 seasonal influenza epidemics.


A total of 541 adults presenting with influenza-like illness for less than 36 hours.


Non-persistence, the time between inclusion and the last dose treated as a failure time, was used as the primary endpoint.


The proportions of patients who persisted on treatment until the end of prescription were estimated at 85.73% (±3.28%) for the oral route and 82.73% (±3.44%) for the inhaled route. Based on multivariable models, non-persistence was associated with a PCR confirmation of influenza for both the oral (HR=0.54, p=0.010) and inhaled (HR=0.59, p=0.018) drugs and antibiotic coprescriptions (HR=2.07, p=0.007; and HR=1.88, p=0.017, respectively) and active combination treatment (HR=1.71, p=0.035; and HR=1.58, p=0.035, respectively). The hazard of non-persistence of the inhaled therapy was increased compared with that of the oral therapy (HR=1.23, p=0.043).


In addition to the clinical and virological profiles of influenza infection, non-persistence may have been influenced by an active combination and the route of administration.


NCT00799760. This is a post-result analysis.


Antiviral Agents; Controlled Clinical Trials; Human Influenza; Medication Non-Adherence; Randomized

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: XD has had a conference invitation from GSK and lecture fees from Roche and Gilead. SVDW has had a conference invitation from GSK, research grant from GSK on unrelated subject, joined patent from institution with GSK on unrelated subject, travel grants for meetings from GSK, contribution to clinical trial financed by Roche, member of the advisory committee on influenza of the French Ministry of Health, is a member of ESWI, is a member of the scientific committee of the GEIG and is vice-president of the GROG network. AM has membership in the ministry of health advisory board on influenza, involvement in some epidemiological studies partially or fully granted by Roche and GSK, and travel grants from Roche for participation in scientific meetings. AM received fees from Roche, preclinical pharmacokinetic department, for a course on MONOLIX in December 2008. BL has had paid consultancy and board membership (Roche, GSK, Novartis, BioCryst, MedImmune), has had research grants from Roche and Sanofi-Pasteur, and had received travel grants and honoraria for speaking or participation at meetings (Roche, Sanofi-Pasteur).

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