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