title: Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain.
  
  
  METHODS
  HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis.
  
  
  CONCLUSIONS
  The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting.
  
  
  BACKGROUND
  ISRCTN91859104.
authors: Division of Rheumatic and Musculoskeletal Disease and National Institute of Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds LS7 4SA, UK.
authors: Sarah R
authors: SR
authors: Kingsbury
authors: Puvan
authors: P
authors: Tharmanathan
authors: Joy
authors: J
authors: Adamson
authors: Nigel K
authors: NK
authors: Arden
authors: Fraser
authors: F
authors: Birrell
authors: Sarah
authors: S
authors: Cockayne
authors: John
authors: J
authors: Dickson
authors: Michael
authors: M
authors: Doherty
authors: Krysia S
authors: KS
authors: Dziedzic
authors: Andrew
authors: A
authors: Grainger
authors: Catherine E
authors: CE
authors: Hewitt
authors: Terence W
authors: TW
authors: O'Neill
authors: David L
authors: DL
authors: Scott
authors: Tonia L
authors: TL
authors: Vincent
authors: Richard J
authors: RJ
authors: Wakefield
authors: Fiona E
authors: FE
authors: Watt
authors: David J
authors: DJ
authors: Torgerson
authors: Philip G
authors: PG
authors: Conaghan
mesh_terms: D000203:Activities of Daily Living; D000700:Analgesics / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D018771:Arthralgia / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D002985:Clinical Protocols; D003365:Costs and Cost Analysis; D004311:Double-Blind Method; D016527:Drug Costs; D050823:Hand Joints / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D016014:Linear Models; D016015:Logistic Models; D015999:Multivariate Analysis; D010003:Osteoarthritis / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D010147:Pain Measurement; D018579:Patient Selection; D011320:Primary Health Care; D011788:Quality of Life; D011859:Radiography; D020127:Recovery of Function; D012107:Research Design; D013585:Synovitis / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D006113:United Kingdom
chemical_list: D000700:Analgesics; D006886:Hydroxychloroquine