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
Open accessAbstract
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).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mice carrying NOX2 deletion treated with high fat diet gain weight but show no increase in ROS production or endothelial dysfunction compared with control animals.
“In these studies, mice carrying the deletion gain weight but show no increase in ROS production or endothelial dysfunction as compared with the control animals (256, 609).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [609]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Altman, R., Carreras, L., Díaz, R. S., Figueroa, E. B., Paolasso, E., Parodi, J. C., Cade, J. F., Donnan, G. A., Eadie, M. J., Gavaghan, T. P., et al. (1994) · BMJ · doi:10.1136/bmj.308.6921.81 · Cited by 4,198 · see citing works
Altman, R., Carreras, L., Díaz, R. S., Figueroa, E. B., Paolasso, E., Parodi, J. C., Cade, J. F., Donnan, G. A., Eadie, M. J., Gavaghan, T. P., et al. (1994) · Cited by 3,322 · see citing works
(1958) · Journal of the American Pharmaceutical Association (Scientific ed ) · doi:10.1002/jps.3030470133 · Cited by 2,491 · see citing works
Uric Acid and Cardiovascular Risk
Feig, D. I., Kang, D., & Johnson, R. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0800885 · Cited by 2,443 · see citing works
Zhang, W., Doherty, M., Bardin, T., Pascual, E., Barskova, V., Conaghan, P. G., Gerster, J., Jacobs, J. W. G., Leeb, B., Lioté, F., et al. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.055269 · Cited by 1,398 · see citing works
Self-citation(1994) · Europe PMC (PubMed Central) · Cited by 755 · see citing works
Khanna, D., Khanna, P. P., FitzGerald, J. D., Singh, M. K., Bae, S. S., Neogi, T., Pillinger, M. H., Merill, J., Lee, S., Prakash, S., et al. (2012) · Arthritis Care & Research · doi:10.1002/acr.21773 · Cited by 725 · see citing works
Schumacher, H. R., Becker, M. A., Wortmann, R. L., MacDonald, P. A., Hunt, B., Streit, J., Lademacher, C., & Joseph‐Ridge, N. (2008) · Arthritis Care & Research · doi:10.1002/art.24209 · Cited by 638 · see citing works
Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study
Kuo, C.-F., Grainge, M. J., Mallen, C. D., et al. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204463 · Cited by 625 · see citing works
Prospective Randomized Open Blinded End-point (PROBE) Study. A novel design for intervention trials
Hansson, L., Hedner, T., & Dahlöf, B. (1992) · Blood Pressure · doi:10.3109/08037059209077502 · Cited by 578 · see citing works
American College of Rheumatology guidelines for management of gout
Khanna, D. (2013) · GOUT AND NUCLEIC ACID METABOLISM · doi:10.6032/gnam.37.139 · Cited by 544 · see citing works
Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005
Annemans, L., Spaepen, E., Gaskin, M., Bonnemaire, M., Malier, V., Gilbert, T., & Nuki, G. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.076232 · Cited by 495 · see citing works
Self-citationGuidelines for good pharmacoepidemiology practices (GPP)
ISPE (2007) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1471 · Cited by 349 · see citing works
Gout therapeutics: new drugs for an old disease
Burns, C. M., & Wortmann, R. L. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60665-4 · Cited by 237 · see citing works
Strasak, A. M., Ruttmann, E., Brant, L. J., Kelleher, C., Klenk, J., Concin, H., Diem, G., Pfeiffer, K. P., Ulmer, H., & and the VHM&PP Study Group (2007) · Clinical Chemistry · doi:10.1373/clinchem.2007.094425 · Cited by 228 · see citing works
Strasak, A. M., Kelleher, C., Brant, L. J., Rapp, K., Ruttmann, E., Concin, H., Diem, G., Pfeiffer, K. P., & Ulmer, H. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2007.11.094 · Cited by 217 · see citing works
Ioachimescu, A. G., Brennan, D. M., Hoar, B. M., Hazen, S. L., & Hoogwerf, B. J. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23121 · Cited by 194 · see citing works
Epidemiology of gout: An update
Smith, E. U. R., Díaz‐Torné, C., Pérez-Ruiz, F., & MARCH, L. M. (2010) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2010.10.004 · Cited by 184 · see citing works
Epidemiology of hyperuricemia and gout.
Luk, A. J., & Simkin, P. A. (2005) · PubMed · Cited by 141 · see citing works
How is Gout Managed in Primary Care? A Review of Current Practice and Proposed Guidelines
Pal, B., Foxall, M., Dysart, T., Carey, F., & Whittaker, M. (2000) · Clinical Rheumatology · doi:10.1007/s100670050005 · Cited by 74 · see citing works
Record‐linkage for pharmacovigilance in Scotland
Evans, J. M. M., & MacDonald, T. M. (1999) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1999.00853.x · Cited by 57 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [5]Wortmann R Kelly's textbook of rheumatology. 8th edn Philadelphia: Saunders, 2009
Cited by
Sorted by citations
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
- Authors
- MacDonald, T. M., Ford, I., Nuki, G., Mackenzie, I. S., De Caterina, R., Findlay, E., Hallas, J., Hawkey, C. J., Ralston, S., Walters, M., Webster, J., McMurray, J., Perez Ruiz, F., & Jennings, C. G.
- Affiliations
- University of Dundee (GB)
- University of Glasgow (GB)
- Western General Hospital (GB)
- University of Southern Denmark (DK)
- University of Nottingham (GB)
- University of Aberdeen (GB)
- Corresponding author
- MacDonald, Thomas M
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2014-07
- Volume
- 4
- Issue
- 7
- Pages
- e005354
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC4120410
- OpenAlex
- W2131167925
- Cited by
- 93
- References
- 21
- Citations by year
- 2024: 3 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 17 · 2019: 13 · 2018: 17 · 2017: 13 · 2016: 7 · 2015: 3 · 2014: 2
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (acceptedVersion, cc-by-nc)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- HighWire Press Open Archive (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion, cc-by-nc)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- Pfizer
- AstraZeneca
- Servier
- Ipsen
- Topics
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- febuxostat, allopurinol, hyperuricemia, gout, xanthine oxidase inhibitors, cardiovascular safety, cardiovascular events, non-inferiority, serum urate target, older adults, cardiovascular risk factors, thrombotic complications, cardiac arrhythmias, heart failure hospitalization, angina pectoris, stroke, myocardial infarction, cardiovascular mortality
- MeSH terms
- Febuxostat, Allopurinol, Cardiovascular Diseases, Gout, Gout Suppressants, Humans, Prospective Studies, Research Design, Hyperuricemia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
