Clinical and virologic effects of four neuraminidase inhibitors in influenza A virus-infected children (aged 4-12 years): an open-label, randomized study in Japan

Expert Rev Anti Infect Ther. 2018 Feb;16(2):173-182. doi: 10.1080/14787210.2018.1421945. Epub 2017 Dec 29.

Abstract

Background: Neuraminidase inhibitors (NAIs) reduce influenza symptoms but clear evidence of relationships between viral titer reduction and symptom alleviation is lacking. This open-label, randomized study evaluated differences in viral dynamics between NAIs, and relationships between viral dynamics and influenza symptoms (trial registration number: UMIN000012670).

Methods: Patients (n = 123) aged 4-12 years with influenza A virus infection were randomized to intravenous peramivir, oral oseltamivir, inhaled zanamivir, or inhaled laninamivir. Patients received regular viral assessments of nasal discharge, at least until rapid antigen tests were negative. Time to virus clearance, based on influenza virus titer, was the primary endpoint.

Results: Peramivir recipients had a significantly shorter time to virus clearance than oseltamivir recipients (adjusted p = 0.035). Comparisons between the peramivir group and other NAI groups were not significant. There were no significant inter-group differences in other clinical efficacy endpoints (time to resolution of fever, time to alleviation of symptoms). However, the peramivir group showed a smaller numerical proportion of relapses with fever or positive virus than the other groups.

Conclusions: The time to virus clearance was significantly shorter with peramivir than with oseltamivir. Although no clear relationship between virus dynamics and symptoms was observed, ongoing studies should clarify the situation.

Keywords: Influenza; UMIN-CTR; neuraminidase inhibitor; peramivir; randomized study; trial registration.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids, Carbocyclic
  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cyclopentanes / therapeutic use
  • Female
  • Guanidines / therapeutic use
  • Humans
  • Influenza A virus / drug effects*
  • Influenza A virus / isolation & purification
  • Influenza, Human / drug therapy*
  • Influenza, Human / virology
  • Japan
  • Male
  • Neuraminidase / antagonists & inhibitors
  • Oseltamivir / therapeutic use
  • Pyrans
  • Sialic Acids
  • Time Factors
  • Treatment Outcome
  • Zanamivir / analogs & derivatives
  • Zanamivir / therapeutic use

Substances

  • Acids, Carbocyclic
  • Antiviral Agents
  • Cyclopentanes
  • Guanidines
  • Pyrans
  • Sialic Acids
  • Oseltamivir
  • laninamivir
  • Neuraminidase
  • Zanamivir
  • peramivir