None listed
Conditions
Brief summary
We are planning a two-year, randomized controlled trial of intensive urate-lowering therapy for erosive gout. The study will recruit 104 participants with erosive gout on oral urate-lowering therapy with serum urate concentrations above the therapeutic target of 0.30mmol/L; participants will be randomly assigned to intensification of oral urate-lowering therapy to maintain serum urate concentration of <0.30mmol/L (5mg/dL, standard management) or <0.20mmol/L (3.3mg/dl, intensive management). Participants will undergo clinical assessment, laboratory testing and radiographic assessment of bone erosion (by CT and plain radiography) at baseline, and after 1 and 2 years. The primary endpoint will be the change from baseline in total CT erosion score, in the intensive target group compared to the standard target group. Other endpoints will include safety outcomes, other measures of structural joint disease and OMERACT endorsed domains for chronic gout studies.
Interventions
Oral urate-lowering therapy for two years to maintain serum urate concentration of <0.20mmol/L (3.3mg/dl, intensive management).
Urate-lowering therapy will be adjusted according to the standardized protocol to reach the target serum urate concentration; <0.20mmol/L. During dose adjustment, serum urate levels will be monitored monthly.
The standardized urate lowering therapy escalation protocol is as follows:
a. For those tolerant to allopurinol, allopurinol will be increased every month by 50-
Oral urate-lowering therapy for two years to maintain serum urate concentration of <0.20mmol/L (3.3mg/dl, intensive management). Urate-lowering therapy will be adjusted according to the standardized protocol to reach the target serum urate concentration; <0.20mmol/L. During dose adjustment, serum urate levels will be monitored monthly. The standardized urate lowering therapy escalation protocol is as follows: a. For those tolerant to allopurinol, allopurinol will be increased every month by 50-100mg daily (increment dependent on eGFR), to a maximum dose of 900mg daily. b. If the treatment target is not reached after one month of maximum tolerated allopurinol monotherapy, probenecid will be added at 500mg twice daily, increasing to 1g twice daily after one month if needed to achieve the target. c. If the treatment target is not reached after one month of maximum tolerated allopurinol/probenecid combination therapy, these treatments will be replaced with febuxostat at 80mg daily, increasing to a maximum dose of 120mg daily. d. If the treatment target is not reached with after one month of maximum tolerated febuxostat, benzbromarone will be started at 100mg daily, in combination with allopurinol if tolerated (at the previously tolerated allopurinol dose). This protocol represents maximal approved dosing of available urate-lowering therapies in New Zealand, and is consistent with the usual clinical practice regarding choice of agents. In the case of previous kidney stones, uricosuric therapy (probenecid and benzbromarone) will not be used. Standard contra-indications according to the datasheet for each agent will also be assessed on an individual patient basis when considering changes to urate-lowering therapy, consistent with best clinical practice. Adherence will be assessed at each study visit by pill count.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Gout, as defined by the 2015 ACR-EULAR classification criteria At least one bone erosion on plain radiographs of the feet Age over 18 years Able to provide informed consent On oral urate-lowering therapy Serum urate concentrations at or above 0.30mmol/L
Exclusion criteria
Stage 4 or 5 chronic kidney disease (estimated glomerular filtration rate (eGFR) <30mls/min/1.73m2) Pregnancy or breastfeeding Unstable systemic medical condition On azathioprine (due to potential interactions with both allopurinol and febuxostat) On warfarin
Outcome results
None listed