A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout

Ann Rheum Dis. 2009 Jun;68(6):892-7. doi: 10.1136/ard.2008.091462. Epub 2008 Jul 16.

Abstract

Objectives: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) < or =0.30 mmol/l (5 mg/dl).

Methods: A randomised, controlled, open-label, multicentre trial in gout patients with renal function defined as a calculated creatinine clearance > or =50 ml/min. Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If sUr < or =0.30 mmol/l was not attained after 2 months, the dose was doubled to allopurinol 300 mg twice a day or benzbromarone 200 mg once a day (stage 2). The primary end point was treatment success in either of the two stages, defined as clinical tolerability and attainment of biochemical target sUr.

Results: Sixty-five patients were enrolled in stage 1; 36 received allopurinol and 29 received benzbromarone. Fifty-five patients (85%) were analysed at stage 1: the success rates were 8/31 (26%) and 13/25 (52%), respectively, and the difference was -0.26 (95% CI from -0.486 to -0.005), p = 0.049. At stage 2, the success rates were 21/27 (78%) and 18/23 (78%), respectively, and the difference was -0.005 (95% CI from -0.223 to 0.220), p = 1.00. Two patients stopped receiving allopurinol and three stopped receiving benzbromarone because of adverse drug reactions.

Conclusions: Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/day according to the target sUr produced significantly higher success rates (both 78% successful in attaining sUr < or =0.30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation.

Trial registration number: ISRCTN49563848).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Allopurinol / administration & dosage*
  • Allopurinol / adverse effects
  • Allopurinol / therapeutic use
  • Benzbromarone / administration & dosage*
  • Benzbromarone / adverse effects
  • Benzbromarone / therapeutic use
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Gout / blood
  • Gout / drug therapy*
  • Gout Suppressants / administration & dosage*
  • Gout Suppressants / adverse effects
  • Gout Suppressants / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Oxypurinol / blood
  • Patient Compliance
  • Prospective Studies
  • Treatment Outcome
  • Uric Acid / blood
  • Uricosuric Agents / administration & dosage*
  • Uricosuric Agents / adverse effects
  • Uricosuric Agents / therapeutic use

Substances

  • Gout Suppressants
  • Uricosuric Agents
  • Uric Acid
  • Benzbromarone
  • Allopurinol
  • Oxypurinol

Associated data

  • ISRCTN/ISRCTN49563848