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.
OBJECTIVE
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.


BACKGROUND
ISRCTN49563848).
Reinders
M K
MK
Department of Pharmacy, University of Groningen, The Netherlands. m.reinders@atriummc.nl
Haagsma
C
C
Jansen
T L Th A
TL
van Roon
E N
EN
Delsing
J
J
van de Laar
M A F J
MA
Brouwers
J R B J
JR
D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001553:Benzbromarone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000097:blood; D010349:Patient Compliance; D011446:Prospective Studies; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D014528:Uricosuric Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D006074:Gout Suppressants; D014528:Uricosuric Agents; D014527:Uric Acid; D001553:Benzbromarone; D000493:Allopurinol; D010117:Oxypurinol