title: Randomized controlled trial of the effect of regular paracetamol on influenza infection.
abstract: 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.
  
  
  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 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.
  
  
  CONCLUSIONS
  Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR-confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection.
  
  
  BACKGROUND
  ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry.
authors.affiliation: Medical Research Institute of New Zealand, New Zealand, Wellington.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jefferies
authors.affiliation: Medical Research Institute of New Zealand, New Zealand, Wellington.
authors.forename: Irene
authors.identifier: http://orcid.org/0000-0001-5327-3027
authors.initials: I
authors.lastname: Braithwaite
authors.affiliation: Medical Research Institute of New Zealand, New Zealand, Wellington.
authors.forename: Steven
authors.initials: S
authors.lastname: Walker
authors.affiliation: Department of Medicine, University of Otago Wellington, New Zealand, Wellington.|Capital & Coast District Health Board, New Zealand, Wellington.
authors.forename: Mark
authors.initials: M
authors.lastname: Weatherall
authors.affiliation: Canterbury Health Laboratories, Canterbury District Health Board, Christchurch, New Zealand.
authors.forename: Lance
authors.initials: L
authors.lastname: Jennings
authors.affiliation: Canterbury Health Laboratories, Canterbury District Health Board, Christchurch, New Zealand.
authors.forename: Michelle
authors.initials: M
authors.lastname: Luck
authors.affiliation: Canterbury Health Laboratories, Canterbury District Health Board, Christchurch, New Zealand.
authors.forename: Kevin
authors.initials: K
authors.lastname: Barrett
authors.affiliation: Department of Medicine, University of Otago Wellington, New Zealand, Wellington.
authors.forename: Robert
authors.initials: R
authors.lastname: Siebers
authors.affiliation: Capital & Coast District Health Board, New Zealand, Wellington.
authors.forename: Timothy
authors.initials: T
authors.lastname: Blackmore
authors.affiliation: Medical Research Institute of New Zealand, New Zealand, Wellington.|Capital & Coast District Health Board, New Zealand, Wellington.
authors.forename: Richard
authors.initials: R
authors.lastname: Beasley
authors.affiliation: Medical Research Institute of New Zealand, New Zealand, Wellington.|Department of Medicine, University of Otago Wellington, New Zealand, Wellington.|Capital & Coast District Health Board, New Zealand, Wellington.
authors.forename: Kyle
authors.initials: K
authors.lastname: Perrin
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D058633:Antipyretics / Q000627:therapeutic use*; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006304:Health Status; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D008297:Male; D009666:Nose / Q000821:virology; D063189:Symptom Assessment; D019562:Viral Load / Q000187:drug effects*; D017201:Virus Shedding / Q000187:drug effects; D055815:Young Adult
chemical_list: D058633:Antipyretics; D000082:Acetaminophen
keywords: anti-pyresis; influenza; influenza-like illness; paracetamol; randomized controlled trial