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

## TL;DR

This study found that higher doses of oseltamivir did not significantly improve outcomes for severe influenza patients on mechanical ventilation.

## Contribution

The study is the first to compare double and triple doses of oseltamivir in mechanically ventilated influenza patients.

## Key findings

- Viral clearance rates were low and similar between double and triple-dose groups after 5 days.
- Triple doses led to faster decline in influenza A viral load but longer hospital stays.
- No significant differences in mortality or ICU outcomes were observed between the two dose groups.

## Abstract

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

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.

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.

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