title: Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established.
  
  
  METHODS
  AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events.
  
  
  CONCLUSIONS
  The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU.
  
  
  BACKGROUND
  The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014).
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. helen.tilbrook@york.ac.uk.
authors.forename: Helen
authors.initials: H
authors.lastname: Tilbrook
authors.affiliation: St George's Vascular Institute, St George's Healthcare NHS Trust, Blackshaw Road, London, SW17 0QT, UK. rachael.forsythe@ed.ac.uk.
authors.forename: Rachael O
authors.initials: RO
authors.lastname: Forsythe
authors.affiliation: St George's University of London, London, UK. drolfe@sgul.ac.uk.
authors.forename: Debbie
authors.initials: D
authors.lastname: Rolfe
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. laura.clark@york.ac.uk.
authors.forename: Laura
authors.initials: L
authors.lastname: Clark
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. martin.bland@york.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Bland
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. hannah.buckley@york.ac.uk.
authors.forename: Hannah
authors.initials: H
authors.lastname: Buckley
authors.affiliation: Hull York Medical School, University of Hull, Kingston upon Hull, UK. ian.chetter@hey.nhs.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Chetter
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. liz.cook@york.ac.uk.
authors.forename: Liz
authors.initials: L
authors.lastname: Cook
authors.affiliation: School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK. jo.dumville@manchester.ac.uk.
authors.forename: Jo
authors.initials: J
authors.lastname: Dumville
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. rhian.gabe@york.ac.uk.
authors.forename: Rhian
authors.initials: R
authors.lastname: Gabe
authors.affiliation: Wound Healing Research Unit, Cardiff University, Cardiff, UK. hardingkg@cf.ac.uk.
authors.forename: Keith
authors.initials: K
authors.lastname: Harding
authors.affiliation: Harrogate and District NHS Foundation Trust, London, UK. alison.layton@hdft.nhs.uk.
authors.forename: Alison
authors.initials: A
authors.lastname: Layton
authors.affiliation: The Lindsay Leg Club Foundation, London, UK. ellie@legclubfoundation.com.
authors.forename: Ellie
authors.initials: E
authors.lastname: Lindsay
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. catriona.mcdaid@york.ac.uk.
authors.forename: Catriona
authors.initials: C
authors.lastname: McDaid
authors.affiliation: School of Health Sciences, University of Nottingham, Nottingham, UK. christine.moffatt@nottingham.ac.uk.
authors.forename: Christine
authors.initials: C
authors.lastname: Moffatt
authors.affiliation: Swansea Centre for Health Economics, Swansea University, Swansea, UK. C.J.Phillips@swansea.ac.uk.
authors.forename: Ceri
authors.initials: C
authors.lastname: Phillips
authors.affiliation: School of Surgical and Reproductive Sciences, Newcastle University, Newcastle upon Tyne, UK. Gerard.Stansby@nuth.nhs.uk.
authors.forename: Gerard
authors.initials: G
authors.lastname: Stansby
authors.affiliation: University of Bradford, Bradford, UK. peter.vowden@mac.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Vowden
authors.affiliation: St George's Vascular Institute, St George's Healthcare NHS Trust, Blackshaw Road, London, SW17 0QT, UK. laurie.williams49@gmail.com.
authors.forename: Laurie
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Health Sciences, York Trials Unit, University of York, York, UK. david.torgerson@york.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Torgerson
authors.affiliation: St George's Vascular Institute, St George's Healthcare NHS Trust, Blackshaw Road, London, SW17 0QT, UK. rhinchli@sgul.ac.uk.|St George's University of London, London, UK. rhinchli@sgul.ac.uk.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hinchliffe
mesh_terms: D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D058128:Compression Bandages; D004311:Double-Blind Method; D004739:England; D005240:Feasibility Studies; D006801:Humans; D057194:Intention to Treat Analysis; D016016:Proportional Hazards Models; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014647:Varicose Ulcer / Q000175:diagnosis / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001241:Aspirin