title: VenUS IV (Venous leg Ulcer Study IV) - compression hosiery compared with compression bandaging in the treatment of venous leg ulcers: a randomised controlled trial, mixed-treatment comparison and decision-analytic model.
abstract: BACKGROUND
  Compression is an effective and recommended treatment for venous leg ulcers. Although the four-layer bandage (4LB) is regarded as the gold standard compression system, it is recognised that the amount of compression delivered might be compromised by poor application technique. Also the bulky nature of the bandages might reduce ankle or leg mobility and make the wearing of shoes difficult. Two-layer compression hosiery systems are now available for the treatment of venous leg ulcers. Two-layer hosiery (HH) may be advantageous, as it has reduced bulk, which might enhance ankle or leg mobility and patient adherence. Some patients can also remove and reapply two-layer hosiery, which may encourage self-management and could reduce costs. However, little robust evidence exists about the effectiveness of two-layer hosiery for ulcer healing and no previous trials have compared two-layer hosiery delivering 'high' compression with the 4LB.
  
  
  OBJECTIVE
  Part I To compare the clinical effectiveness and cost-effectiveness of HH and 4LB in terms of time to complete healing of venous leg ulcers. Part II To synthesise the relative effectiveness evidence (for ulcer healing) of high-compression treatments for venous leg ulcers using a mixed-treatment comparison (MTC). Part III To construct a decision-analytic model to assess the cost-effectiveness of high-compression treatments for venous leg ulcers.
  
  
  METHODS
  Part I A multicentred, pragmatic, two-arm, parallel, open randomised controlled trial (RCT) with an economic evaluation. Part II MTC using all relevant RCT data - including Venous leg Ulcer Study IV (VenUS IV). Part III A decision-analytic Markov model.
  
  
  METHODS
  Part I Community nurse teams or services, general practitioner practices, leg ulcer clinics, tissue viability clinics or services and wound clinics within England and Northern Ireland.
  
  
  METHODS
  Part I Patients aged ≥ 18 years with a venous leg ulcer, who were willing and able to tolerate high compression.
  
  
  METHODS
  Part I Participants in the intervention group received HH. The control group received the 4LB, which was applied according to standard practice. Both treatments are designed to deliver 40 mmHg of compression at the ankle. Part II and III All relevant high-compression treatments including HH, the 4LB and the two-layer bandage (2LB).
  
  
  METHODS
  Part I The primary outcome measure was time to healing of the reference ulcer (blinded assessment). Part II Time to ulcer healing. Part III Quality-adjusted life-years (QALYs) and costs.
  
  
  RESULTS
  Part I A total of 457 participants were recruited. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.79 to 1.25; p = 0.96]. Time to ulcer recurrence was significantly shorter in the 4LB group (HR = 0.56, 95% CI 0.33 to 0.94; p = 0.026). In terms of cost-effectiveness, using QALYs as the measure of benefit, HH had a > 95% probability of being the most cost-effective treatment based on the within-trial analysis. Part II The MTC suggests that the 2LB has the highest probability of ulcer healing compared with other high-compression treatments. However, this evidence is categorised as low to very low quality. Part III Results suggested that the 2LB had the highest probability of being the most cost-effective high-compression treatment for venous leg ulcers.
  
  
  CONCLUSIONS
  Trial data from VenUS IV found no evidence of a difference in venous ulcer healing between HH and the 4LB. HH may reduce ulcer recurrence rates compared with the 4LB and be a cost-effective treatment. When all available high-compression treatments were considered, the 2LB had the highest probability of being clinically effective and cost-effective. However, the underpinning evidence was sparse and more research is needed. Further research should thus focus on establishing, in a high-quality trial, the effectiveness of this compression system in particular.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN49373072.
  
  
  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. 18, No. 57. See the NIHR Journals Library website for further project information.
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Ashby
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: Rhian
authors.initials: R
authors.lastname: Gabe
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Ali
authors.affiliation: Centre for Health Economics, The University of York, York, UK.
authors.forename: Pedro
authors.initials: P
authors.lastname: Saramago
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: Ling-Hsiang
authors.initials: LH
authors.lastname: Chuang
authors.affiliation: School of Healthcare, The University of Leeds, Leeds, UK.
authors.forename: Una
authors.initials: U
authors.lastname: Adderley
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bland
authors.affiliation: School of Nursing, Midwifery and Social Work, The University of Manchester, Manchester, UK.
authors.forename: Nicky A
authors.initials: NA
authors.lastname: Cullum
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: Jo C
authors.initials: JC
authors.lastname: Dumville
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: Cynthia P
authors.initials: CP
authors.lastname: Iglesias
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Kang'ombe
authors.affiliation: Centre for Health Economics, The University of York, York, UK.
authors.forename: Marta O
authors.initials: MO
authors.lastname: Soares
authors.affiliation: St Mary's Hospital, Leeds, UK.
authors.forename: Nikki C
authors.initials: NC
authors.lastname: Stubbs
authors.affiliation: Department of Health Sciences, The University of York, York, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Torgerson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058128:Compression Bandages / Q000009:adverse effects / Q000191:economics / Q000706:statistics & numerical data*; D003362:Cost-Benefit Analysis; D003657:Decision Making; D004739:England; D005260:Female; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009660:Northern Ireland; D010043:Outcome and Process Assessment, Health Care / Q000191:economics / Q000706:statistics & numerical data; D010349:Patient Compliance; D019057:Quality-Adjusted Life Years; D012008:Recurrence; D055502:Secondary Prevention / Q000379:methods*; D012648:Self Care; D053828:Stockings, Compression / Q000009:adverse effects / Q000191:economics / Q000706:statistics & numerical data; D013997:Time Factors; D014647:Varicose Ulcer / Q000191:economics / Q000628:therapy*; D014945:Wound Healing