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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
  1. M K Reinders1,2,
  2. C Haagsma3,
  3. T L Th A Jansen4,
  4. E N van Roon1,2,
  5. J Delsing5,
  6. M A F J van de Laar5,6,
  7. J R B J Brouwers1,2
  1. 1
    Department of Pharmacy, Division of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands
  2. 2
    Department of Clinical Pharmacy and Pharmacology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands
  3. 3
    Department of Rheumatology, Ziekenhuisgroep Twente, Almelo, The Netherlands
  4. 4
    Department of Rheumatology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands
  5. 5
    Department of Rheumatology, Medisch Spectrum Twente, Enschede, The Netherlands
  6. 6
    University Twente, Enschede, The Netherlands
  1. Mr M K Reinders, Department of Clinical Pharmacy, Atrium Medisch Centrum Parkstad, PO Box 4446, 6401 CX Heerlen, The Netherlands; m.reinders{at}


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) ⩽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 ⩾50 ml/min. Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If sUr ⩽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 ⩽0.30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation.

Trial registration number: ISRCTN49563848).

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  • Competing interests: None.

  • Ethics approval: Obtained.

  • Patient consent: Obtained.

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