Randomized controlled trial of the effect of regular paracetamol on influenza infection

Jefferies, Sarah; Braithwaite, Irene; Walker, Steven; Weatherall, Mark; Jennings, Lance; Luck, Michelle; Barrett, Kevin; Siebers, Robert; Blackmore, Timothy; Beasley, Richard; Perrin, Kyle

There are a number of alternative explanations for our finding of no difference between randomized groups apart from that, in fact, paracetamol does not affect influenza outcomes. The study did not recruit 80 PCR-confirmed cases despite screening with a rapid antigen testing kit with a reported diagnostic specificity of 96-100% for both influenza A and B. 23 All Baseline pernasal samples contained human RNA, indicating that this lower than expected result was unlikely to be due to poor sampling technique. It is possible that the specificity of the rapid antigen test was reduced in this study due to cross reactivity with other respiratory viruses. 23 The lower than anticipated number of PCR-positive influenza cases might be expected to reduce statistical power to detect differences, but the SD of the primary outcome variable was substantially less than anticipated from past research. The CI for the difference excluded the difference we expected to detect, that is half the magnitude of that seen with anti-viral treatment of influenza, 27 but it may be that a smaller difference in the primary outcome variable is still clinically relevant. In terms of the clinical outcome variables, paracetamol did not have any significant anti-pyretic effect whether measured as daily maximum, daily mean or AUC of temperature over 48 h. This may be due in part to the modest febrile response in the participants, the mean maximum temperature on Day 1 in the influenza PCR-positive group was 38.1°C, falling to 37.4°C by Day 2. Due to its lack of anti-pyretic efficacy in our sample, we were unable to test our hypothesis that the suppression of fever with paracetamol in influenza infection may be harmful.