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

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

Abstract: Editor's Choice ORIGINAL ARTICLE Randomized controlled trial of the effect of regular paracetamol on influenza infection SARAH JEFFERIES, 1 IRENE BRAITHWAITE, 1 STEVEN WALKER, 1 MARK WEATHERALL, 2,3 LANCE JENNINGS, 4 MICHELLE LUCK, 4 KEVIN BARRETT, 4 ROBERT SIEBERS, 2 TIMOTHY BLACKMORE, 3 RICHARD BEASLEY 1,3 AND KYLE PERRIN 1,2,3 On behalf of the Pi Study Group* 1 Medical Research Institute of New Zealand, 2 Department of Medicine, University of Otago Wellington, 3 Capital & Coast District Health Board, Wellington, and 4 Canterbury Health Laboratories, Canterbury District Health Board, Christchurch, New Zealand ABSTRACT Background and objective: Anti-pyretic treatment is recommended in the management of influenza infection. In animal models anti-pyretic treatment increases mortality from influenza.We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection. Methods: This is a randomized, double-blind, placebo-controlled trial of adults aged 18-65 years with influenza-like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT-PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5-14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log10 viral load from Baseline to Day 5. Correspondence: Irene Braithwaite, Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington 6242, New Zealand. Email: irene.braithwaite@mrinz.ac.nz Disclosure statement: RB has been a member of the GlaxoSmithKline (GSK) New Zealand advisory board and has received research grants, payments for lectures and/or attended meetings from GSK, a manufacturer of paracetamol. LJ has received unrestricted research funding from F. Hoffman-La Roche, and honoraria and travel assistance from F. Hoffman-La Roche, GlaxoSmithKline and Sanofi Pasteur for participating on advisory groups or in scientific meetings. *Pi Study Group: Medical Research Institute of New Zealand: Irene Braithwaite, Richard Beasley, James Fingleton, Sarah Jefferies, Mark Holliday, Claire Munro, Mitesh Patel, Kyle Perrin, Janine Pilcher, Alison Pritchard and Steve Walker; Capital & Coast District Health Board: Jonathon Barrett, Tim Blackmore, Marina Dzhelali, Leeanne Olsen, Serena Rooker and Helen White; University of Otago, Wellington: Rob Siebers and Mark Weatherall; Canterbury Health Laboratories: Kevin Barratt, Lance Jennings and Michelle Luck. Received 8 April 2015; invited to revise 21 May and 3 July 2015; revised 26 May and 14 July 2015; accepted 31 August 2015 (Associate Editor: Marcos Restrepo). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Article first published online: 6 December 2015 SUMMARY AT A GLANCE Despite recommendations to administer paracetamol for symptom relief in influenza and influenzalike-illnesses, this study has found that regular administration of paracetamol has no effect on viral or clinical outcomes in this setting. Results: A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days.There were 22 and 24..

DOI record: { "DOI": "10.1111/resp.12685", "ISSN": [ "1323-7799", "1440-1843" ], "URL": "http://dx.doi.org/10.1111/resp.12685", "abstract": "AbstractBackground and objectiveAnti‐pyretic treatment is recommended in the management of influenza infection. In animal models anti‐pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection.MethodsThis is a randomized, double‐blind, placebo‐controlled trial of adults aged 18–65 years with influenza‐like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT‐PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5–14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log10 viral load from Baseline to Day 5.ResultsA total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR‐positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log10 viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR.ConclusionRegular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR‐confirmed influenza. 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