Becker 2010.

Methods	Randomized, double‐blind, allopurinol‐controlled. 6‐month multicentre study. Stratification by renal function ( normal, mildly impaired = eCLcr 60 to 89 ml/min, or moderately impaired = eCLcr 30 to 59 ml/min) and prior completion of either of two open‐label febuxostat or febuxostat/allopurinol extension trials. No of patients randomised = 2269. No of patients analysed (modified intent‐to‐treat cohort) = 2268 ( one subject randomised to allopurinol was excluded from the efficacy analyses because baseline sUA was < 8.0 mg/dL).
Participants	Inclusion criteria: preliminary criteria of the ACR for gout, serum uric acid of ≥ 8.0 mg/dL, age 18‐85. Subjects successfully completing either of two prior open label extension studies were eligible (subjects from FACT, FOCUS, APEX were eligible for one of these two open label studies) . Exclusion criteria: secondary hyperuricaemia; xanthinuria; severe renal dysfunction (eCLcr < 30 ml/min);hepatic dysfunction (ALT and AST > 1.5 times upper limit of normal);consumption of more than 14 alcoholic drinks per week or a history of alcoholism or drug abuse within five years;or a medical condition that, in the investigator's opinion, would interfere with treatment, harms, or adherence to the protocol. Location: centres in the USA.
Interventions	Patient randomised to 3 groups: 1. Febuxostat 40 mg/day N = 757 2. Febuxosatat 80 mg/day N = 756 3. Allopurinol 200/300 mg (for moderately impaired/ normal to mildly impaired renal function respectively) N = 755 (145/610) [modified intent‐to‐treat cohort]. 30‐day washout period before randomisation for subjects already on uric acid‐lowering therapy. Prophylaxis with naproxen (250 mg BID) or colchicine (0.6 mg daily) given to all subjects during the washout period and the study period (6 months). All subjects receiving naproxen prophylaxis also received lansoprazole 15 mg daily. Subjects with eCLcr < 50 ml/min were not to receive naproxen. Gout flares were regarded as expected gout manifestations rather than as AEs. Serum uric acid was blinded after baseline determination at Day‐4.
Outcomes	The primary efficacy endpoint: ‐ serum uric acid < 6.0 mg/dL at the final visit. Treatment with febuxostat 40 mg was compared with allopurinol with regard to non‐inferiority in uric acid lowering. If non‐inferiority of febuxostat 40 mg was established, superiority to allopurinol was to be assessed. Treatment with febuxostat 80 mg was compared with the allopurinol and febuxostat 40 mg for superiority. "In subgroup analyses, the primary endpoint was stratified by baseline serum uric acid, renal functional status, presence of tophi at baseline, and prior participation in a ULT trial" Secondary efficacy endpoints: ‐ patients with renal impairment and serum uric acid < 6.0 mg/dL at the final visit. ‐ patients with serum uric acid < 6.0mg/dL, < 5.0mg/dL, < 4.0mg/dL at each visit. Pairwise comparisons were made between treatment groups. Adverse events.
Notes	Source of funding: TAP Pharmaceutical Products, Inc.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Authors stated that "An Interactive Voice Response System was utilized by site personnel during screening visits to initiate double blind randomisation. Subjects were randomised 1:1:1 on Day 1 to receive daily febuxostat 40 mg, febuxostat 80 mg, or allopurinol".
Allocation concealment (selection bias)	Low risk	No details provided, but considered probable due to randomisation type.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	No details provided other than stating that this is a double‐blind trial
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only one subject out of 2268 was not included in the efficacy analysis because his serum uric acid was < 8 mg/dL; the rest included in a modified ITT analysis.
Selective reporting (reporting bias)	Unclear risk	The study protocol is not available, but the authors did not report on 5 of the 9 outcomes recommended by OMERACT (OMERACT 9).
Other bias	Low risk	Source of funding: TAP Pharmaceutical Products, Inc.