title: Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia.
abstract: BACKGROUND
  Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST).
  
  
  METHODS
  FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3.
  
  
  BACKGROUND
  FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal.
  
  
  BACKGROUND
  FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).
authors.affiliation: Medicines Monitoring Unit (MEMO), Ninewells Hospital, University of Dundee, Dundee, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: MacDonald
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK.
authors.forename: George
authors.initials: G
authors.lastname: Nuki
authors.affiliation: Medicines Monitoring Unit (MEMO), Ninewells Hospital, University of Dundee, Dundee, UK.
authors.forename: Isla S
authors.initials: IS
authors.lastname: Mackenzie
authors.affiliation: Cardiovascular Division, SS Annunziata Hospital, and Center of Excellence on Aging (Ce.S.I), G d'Annunzio University, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Medicines Monitoring Unit (MEMO), Ninewells Hospital, University of Dundee, Dundee, UK.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Findlay
authors.affiliation: University of Southern Denmark, Odense, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.affiliation: NDDC, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hawkey
authors.affiliation: Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Ralston
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Walters
authors.affiliation: School of Medicine, University of Aberdeen, Aberdeen, UK.
authors.forename: John
authors.initials: J
authors.lastname: Webster
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.affiliation: Rheumatology Division, Hospital de Cruces, Vizcaya, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Perez Ruiz
authors.affiliation: Medicines Monitoring Unit (MEMO), Ninewells Hospital, University of Dundee, Dundee, UK.
authors.forename: Claudine G
authors.initials: CG
authors.lastname: Jennings
mesh_terms: D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D000069465:Febuxostat / Q000009:adverse effects / Q000627:therapeutic use*; D006073:Gout / Q000188:drug therapy* / Q000209:etiology; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D012107:Research Design
chemical_list: D006074:Gout Suppressants; D000069465:Febuxostat; D000493:Allopurinol
keywords: Allopurinol; Cardiovascular Safety; Clinical Trial; Febuxostat