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Chest. 2016 Nov 21. pii: S0012-3692(16)62393-0. doi: 10.1016/j.chest.2016.11.012. [Epub ahead of print]
Efficacy of clarithromycin-naproxen-oseltamivir combination in the treatment of patients hospitalized for influenza A(H3N2) infection: an open-label, randomized controlled, phase 2b/3 trial.
**** IF1, To KK2, Chan JF2, Cheng VC2, Liu KS3, Tam A3, Chan TC3, Zhang AJ2, Li P2, Wong TL2, Zhang R3, Cheung MK3, Leung W4, Lau JY2, Fok M2, Chen H5, Chan KH2, Yuen KY6.
Author information
Abstract
BACKGROUND:
Influenza causes excessive hospitalizations and deaths. Single agent treatment with oseltamivir in severe influenza might be insufficient. The study assessed the efficacy and safety of oseltamivir-clarithromycin-naproxen combination for treatment of serious influenza.
METHODS:
From 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 500mg, naproxen 200mg and oseltamivir 75mg twice daily, followed by 3 days of oseltamivir; or oseltamivir 75mg twice daily without placebos for 5 days as control (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 by pyrosequencing, pneumonia-severity-index (PSI), and duration of hospital-stay.
RESULTS:
Among the 217 influenza A(H3N2) patients enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years and 56% were men. Adverse events were uncommon. Ten patients succumbed during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P=0.01), less frequent ICU/HDU admission (P<0.001), and shorter hospital-stay (P<0.0001). The virus titer, PSI (day 1-3;P<0.01), and NPA specimens with NIRV quasispecies ≥5% (day 1-2;P<0.01) 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 (odds-ratio:0.06; 95%,confidence-interval, 0.004-0.94;P=0.04).
CONCLUSIONS:
Combination treatment reduced both 30- and 90-day mortality and length of hospital-stay. Further study on the antiviral and immunomodulatory effects of this combination treatment for severe influenza is warranted.
Copyright © 2016. Published by Elsevier Inc.
PMID: 27884765 DOI: 10.1016/j.chest.2016.11.012
[PubMed - as supplied by publisher]
Efficacy of clarithromycin-naproxen-oseltamivir combination in the treatment of patients hospitalized for influenza A(H3N2) infection: an open-label, randomized controlled, phase 2b/3 trial.
**** IF1, To KK2, Chan JF2, Cheng VC2, Liu KS3, Tam A3, Chan TC3, Zhang AJ2, Li P2, Wong TL2, Zhang R3, Cheung MK3, Leung W4, Lau JY2, Fok M2, Chen H5, Chan KH2, Yuen KY6.
Author information
Abstract
BACKGROUND:
Influenza causes excessive hospitalizations and deaths. Single agent treatment with oseltamivir in severe influenza might be insufficient. The study assessed the efficacy and safety of oseltamivir-clarithromycin-naproxen combination for treatment of serious influenza.
METHODS:
From 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 500mg, naproxen 200mg and oseltamivir 75mg twice daily, followed by 3 days of oseltamivir; or oseltamivir 75mg twice daily without placebos for 5 days as control (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 by pyrosequencing, pneumonia-severity-index (PSI), and duration of hospital-stay.
RESULTS:
Among the 217 influenza A(H3N2) patients enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years and 56% were men. Adverse events were uncommon. Ten patients succumbed during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P=0.01), less frequent ICU/HDU admission (P<0.001), and shorter hospital-stay (P<0.0001). The virus titer, PSI (day 1-3;P<0.01), and NPA specimens with NIRV quasispecies ≥5% (day 1-2;P<0.01) 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 (odds-ratio:0.06; 95%,confidence-interval, 0.004-0.94;P=0.04).
CONCLUSIONS:
Combination treatment reduced both 30- and 90-day mortality and length of hospital-stay. Further study on the antiviral and immunomodulatory effects of this combination treatment for severe influenza is warranted.
Copyright © 2016. Published by Elsevier Inc.
PMID: 27884765 DOI: 10.1016/j.chest.2016.11.012
[PubMed - as supplied by publisher]