title: Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial 'in hibernation', ready for rapid activation.
abstract: BACKGROUND
  There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias.
  
  
  OBJECTIVE
  To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic.
  
  
  METHODS
  Multicentre, pragmatic, blinded, randomised placebo-controlled trial.
  
  
  METHODS
  Thirty to 40 hospitals in the UK.
  
  
  METHODS
  Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic.
  
  
  METHODS
  Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission.
  
  
  METHODS
  Admission to Intensive Care Unit, or death, within 30 days of admission to hospital.
  
  
  RESULTS
  This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified.
  
  
  CONCLUSIONS
  This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12.
  
  
  BACKGROUND
  This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.
authors.affiliation: Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Wei Shen
authors.initials: WS
authors.lastname: Lim
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Brittain
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Lelia
authors.initials: L
authors.lastname: Duley
authors.affiliation: British Thoracic Society, London, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Edwards
authors.affiliation: School of Tropical Medicine, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Montgomery
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nguyen-Van-Tam
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Read
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Whitham
authors.affiliation: School of Economics, University of Nottingham, Nottingham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Whynes
authors.affiliation: Respiratory Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodhead
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Dan
authors.initials: D
authors.lastname: Wootton
mesh_terms: D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D058873:Pandemics; D012107:Research Design
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone