• Hung Ivan F N IFN Carol Yu Centre for Infection and Division of Infectious Diseases, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, the, To Kelvin K W KKW Carol Yu Centre for Infection and Division of Infectious Diseases, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, the, Chan Jasper F W JFW Carol Yu Centre for Infection and Division of Infectious Diseases, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, t, Cheng Vincent C C VCC Carol Yu Centre for Infection and Division of Infectious Diseases, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology,, Kevin S H Liu, Anthony Tam, Tuen-Ching Chan, Anna Jinxia Zhang, Patrick Li, Tin-Lun Wong, Ricky Zhang, Michael K S Cheung, William Leung, Johnson Y N Lau, Manson Fok, Honglin Chen, Kwok-Hung Chan, and Kwok-Yung Yuen.
• Carol Yu Centre for Infection and Division of Infectious Diseases, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, the University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China; Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
• Chest. 2017 May 1; 151 (5): 1069-1080.

BackgroundInfluenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza.MethodsFrom February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay.ResultsAmong the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04).ConclusionsCombination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted.Trial RegistryBioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879.Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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