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

IntroductionGout 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 analysisFAST 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 disseminationFAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal.Trial Registration numberFAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).

New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert

“…Similarly, the European Medicines Agency (EMA) requested a post-licensing CV safety study comparing febuxostat to allopurinol in gout, termed FAST: febuxostat versus allopurinol streamlined trial. This RCT is ongoing in the UK and Denmark (15). An ongoing RCT in Japan is distinct, in large part, by studying patients with asymptomatic hyperuricemia (FREED: febuxostat for cerebral and cardio-renovascular events prevention study)(16)(Table 1).…”

“…Similarly, the European Medicines Agency requested a post-licensing CV safety study comparing febuxostat to allopurinol in gout, termed the Febuxostat versus Allopurinol Streamlined Trial (FAST). This RCT is ongoing in the UK and Denmark (15). An ongoing RCT in Japan (Febuxostat for Cerebral and Cardiorenovascular Events Prevention Study [FREED]) (16) is distinct, in large part, in that the study population consists of patients with asymptomatic hyperuricemia (Table 1).…”

The future of febuxostat after the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial: who CARES?

“…The ongoing CV outcome trials with febuxostat, i.e. the Febuxostat versus Allopurinol Streamlined Trial (FAST) (in patients aged >60 years with symptomatic hyperuricaemia on allopurinol) [31] and the Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy (FREED) (in patients aged ≥65 years with asymptomatic hyperuricaemia)…”

Odense Pharmacoepidemiological Database: A Review of Use and Content

“…One such example is the clinical descriptive study of heavy users of sumatriptan mentioned above, where identification of patients in OPED allowed supplement with additional data from other sources. Recently, OPED has been used to identify persons who are chronic users of NSAIDs or allopurinol, with the purpose of recruiting participants to large pragmatic trials of drug safety conducted by the Phase IV unit at the University of Southern Denmark .…”