Pharmacodynamic Effect of Different Dosage Regimes of Oseltamivir in Severe Influenza Patients Requiring Mechanical Ventilation: A Multicentre Randomised Controlled Trial

Abstract

Background and Objectives

This randomised controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in severe influenza patients requiring invasive mechanical ventilation.

Methods

Forty intubated adult patients with severe influenza A or B from four intensive care units in Hong Kong were enrolled and randomised to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for 10 days. Baseline data were collected, and outcomes were assessed daily using SOFA and Murray scores. Viral RNA was quantified from nasopharyngeal and tracheal aspirates. The primary outcome was the viral clearance rate after 5 days of treatment; secondary outcomes included 28-day and hospital mortality rates, changes in viral load, and serial SOFA and Murray scores.

Results

Viral clearance rates after 5 days of treatment were low and similar between the double (3/20, 15%) and triple-dose groups (2/20, 10%). No significant differences were observed in 28-day mortality, hospital mortality, ICU length of stay or duration of mechanical ventilation between the double and triple-dose groups. However, patients receiving triple doses exhibited a faster decline in influenza A viral load but had a longer hospital length of stay.

Conclusions

Triple doses of oseltamivir did not significantly improve virological or clinical outcomes compared with double doses in severe influenza.