Pharmacodynamic effect of different dosage regimes of oseltamivir in severe influenza patients requiring mechanical ventilation: a multi-centre randomised controlled trial.

Background: and objectives: This randomized controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in critically ill 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 randomized to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for ten 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 five 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 five days of treatment were low and similar between the double (15%) and triple-dose groups (10%). No significant differences were observed in 28-day mortality, hospital mortality, ICU or hospital 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. Conclusions: Triple doses of oseltamivir did not significantly improve virological or clinical outcomes compared to double doses in severe influenza.