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Trial registered on ANZCTR


Registration number
ACTRN12615001219572
Ethics application status
Approved
Date submitted
3/11/2015
Date registered
9/11/2015
Date last updated
7/06/2021
Date data sharing statement initially provided
22/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized controlled trial of intensive urate-lowering therapy for bone erosion in tophaceous gout
Scientific title
A randomized controlled trial of intensive urate-lowering therapy for bone erosion in tophaceous gout
Secondary ID [1] 287770 0
Nil known
Universal Trial Number (UTN)
U1111-1170-808
Trial acronym
NA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
gout 296656 0
Condition category
Condition code
Musculoskeletal 296879 296879 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 296896 296896 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 293164 0
Treatment: Drugs
Comparator / control treatment
Oral urate-lowering therapy for two years to maintain serum urate concentration of <0.30mmol/L (5mg/dl, intensive management).

Urate-lowering therapy will be adjusted according to the standardized protocol to reach the target serum urate concentration; <0.30mmol/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.
Control group
Active

Outcomes
Primary outcome [1] 296482 0
Change from baseline in total CT erosion score, in the intensive target group compared to the standard target group
Timepoint [1] 296482 0
Baseline, one year and two years
Secondary outcome [1] 318572 0
Frequency of adverse events, including serious adverse events.

Adverse events and serious adverse events will be recorded and reported according to the CTCAE classification.
Timepoint [1] 318572 0
Baseline, one year and two years
Secondary outcome [2] 318573 0
Mean serum urate concentration
Timepoint [2] 318573 0
Baseline, one year and two years
Secondary outcome [3] 318574 0
Percentage of participants with allocated serum urate target achieved
Timepoint [3] 318574 0
Baseline, one year and two years
Secondary outcome [4] 318575 0
Change from baseline in the gout plain radiographic damage index score
Timepoint [4] 318575 0
Baseline, one year and two years

Eligibility
Key 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
Minimum age
19 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2016
Actual
7/03/2016
Date of last participant enrolment
Anticipated
Actual
28/06/2018
Date of last data collection
Anticipated
30/06/2020
Actual
30/06/2020
Sample size
Target
104
Accrual to date
Final
104
Recruitment outside Australia
Country [1] 7285 0
New Zealand
State/province [1] 7285 0
Auckland

Funding & Sponsors
Funding source category [1] 292308 0
Government body
Name [1] 292308 0
Health Research Council of New Zealand
Country [1] 292308 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
85 Park Rd
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 290988 0
None
Name [1] 290988 0
Address [1] 290988 0
Country [1] 290988 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293781 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 293781 0
New Zealand Ministry of Health, Unisys Building, 650 Great South Road, Penrose, Auckland 1051
Ethics committee country [1] 293781 0
New Zealand
Date submitted for ethics approval [1] 293781 0
Approval date [1] 293781 0
11/08/2015
Ethics approval number [1] 293781 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61270 0
Prof Nicola Dalbeth
Address 61270 0
Rheumatologist and Professor
Bone and Joint Research Group
Department of Medicine
Faculty of Medical and Health Sciences
University of Auckland
85 Park Rd, Grafton, Auckland 1023
Country 61270 0
New Zealand
Phone 61270 0
+64 (0) 9 9232568
Fax 61270 0
+64 (0) 9 3737677
Email 61270 0
[email protected]
Contact person for public queries
Name 61271 0
Thrishilia Parshu Ram
Address 61271 0
Bone and Joint Research Group
Department of Medicine
Faculty of Medical and Health Sciences
University of Auckland
85 Park Rd, Grafton, Auckland 1023
Country 61271 0
New Zealand
Phone 61271 0
+64 9 923 3133
Fax 61271 0
+64 9 923 2375
Email 61271 0
[email protected]
Contact person for scientific queries
Name 61272 0
Nicola Dalbeth
Address 61272 0
Bone and Joint Research Group
Department of Medicine
Faculty of Medical and Health Sciences
University of Auckland
85 Park Rd, Grafton, Auckland 1023
Country 61272 0
New Zealand
Phone 61272 0
+64 (0) 9 9232568
Fax 61272 0
+64 (0) 9 3737677
Email 61272 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This was not included in our initial ethical approval, so that further permission from the ethics committee will be sought prior to release of the IPD.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIntensive Serum Urate Lowering With Oral Urate-Lowering Therapy for Erosive Gout: A Randomized Double-Blind Controlled Trial.2022https://dx.doi.org/10.1002/art.42055
N.B. These documents automatically identified may not have been verified by the study sponsor.