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. Issue 7 (10th July 2014)

• Record Type: Journal Article
• Authors: MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G
• Other Names: MacDonald Thomas author non-byline.; Ford Ian author non-byline.; Nuki George author non-byline.; Mackenzie Isla author non-byline.; Hallas Jesper author non-byline.; Webster John author non-byline.; Walters Matthew author non-byline.; Ralston Stuart author non-byline.; Hawkey Chris author non-byline.; De Caterina Raffaele author non-byline.; Perez-Ruiz Fernando author non-byline.; Findlay Evelyn author non-byline.; McMurray John author non-byline.; Maseri Attilio author non-byline.; Murray Gordon author non-byline.; Bird Howard author non-byline.; McMurray John author non-byline.; Petrie Mark author non-byline.; MacDonald Michael author non-byline.; Jhund Pardeep author non-byline.; Saywood Wendy author non-byline.; Flynn Rob author non-byline.; Ford Ian author non-byline.; Kean Sharon author non-byline.
• Is Part Of: BMJ open. Volume 4:Issue 7(2014)
• Publication Date: 2014-07-10
• Subjects: Cardiovascular Safety -- Clinical Trial -- Allopurinol -- Febuxostat; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2014-005354
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: 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 and analysis: 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. Ethics and dissemination: FAST (ISRCTN72443728 ) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. Trial Registration number: 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 ).