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Trial registered on ANZCTR


Trial ID
ACTRN12611000845932
Ethics application status
Approved
Date submitted
27/07/2011
Date registered
10/08/2011
Date last updated
1/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and efficacy of high dose allopurinol in the management of gout: a randomised interventional study
Scientific title
Safety and efficacy of high dose allopurinol in the management of gout: a randomised interventional study
Secondary ID [1] 262717 0
Pilot study registration ACTRN12606000276550
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 270425 0
Condition category
Condition code
Inflammatory and Immune System 270566 270566 0 0
Other inflammatory or immune system disorders
Musculoskeletal 270571 270571 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised open interventional clinical trial. Patients with gout and serum urate greater than or equal to 0.36mmol/L receiving at least the creatinine clearance (CrCL)-based allopurinol dose will be recruited. Patient will be randomised to either continue the current standard of care CrCL-based dose of allopurinol (controls) or undergo allopurinol dose escalation. At 12 months control patients on the CrCL-based allopurinol dose with SU>0.36mmol/L will enter the dose escalation arm of the study (pending an interim safety analysis). All patients will have three-monthly study visits.
Allopurinol dose escalation protocol: There will be 2 phases; Phase 1: Achieving the target SU and Phase 2: Maintaining target SU. In Phase 1, allopurinol will be increased by 50-100mg every month until the target SU <0.36mmol/l is achieved. In addition to the study visits every three months, a monthly blood test will be taken and follow-up phone call to assess side effects in the intervening months. These monthly blood tests will continue until patients have achieved three consecutive monthly visits with a SU <0.36mmol/L. At this point Phase 2 will commence and patients will be seen three monthly until they have completed 24 months from baseline. If the serum urate increases above target in phase 2 the allopurinol dose may be increased
Allopurinol will be taken daily by oral tablet
Intervention code [1] 267061 0
Treatment: drugs
Comparator / control treatment
Controls will continue the current standard of care CrCL-based dose of allopurinol. At 12 months control patients on the CrCL-based allopurinol dose with SU>0.36mmol/L will enter the dose escalation arm of the study
Control group
Dose comparison

Outcomes
Primary outcome [1] 269311 0
Reduction in serum urate from baseline
Timepoint [1] 269311 0
12 and 24 months
Primary outcome [2] 269312 0
occurrence of allopurinol related adverse effects
Adverse effects include abnormal liver function tests and rash. Standardised questions related to adverse events and blood test will be undertaken to detect adverse events. All adverse events will be recorded using CTCAE codes
Timepoint [2] 269312 0
12 and 24 months
Secondary outcome [1] 279348 0
number of gouty attacks as reported by the patient
Timepoint [1] 279348 0
12 and 24 months
Secondary outcome [2] 279349 0
health related quality of life as assessed by Health Assessment Questionnaire (HAQ)
Timepoint [2] 279349 0
12 and 24 months
Secondary outcome [3] 279350 0
plasma oxypurinol concentrations
Timepoint [3] 279350 0
12 and 24 months
Secondary outcome [4] 287558 0
Tophus size as mesured by vernier callipers and digital photography
Timepoint [4] 287558 0
12 and 24 months
Secondary outcome [5] 287559 0
urate burden or bone erosion in patients with gout using plain radiographs of the hands and feet, DEXA scan and CT scans of the feet taken at baseline and on an annual basis. These images will be scored according to protocols we have validated
Timepoint [5] 287559 0
12 and 24 months

Eligibility
Key inclusion criteria
Patients with gout, as defined by the American College of Rheumatology Criteria, receiving at least the CrCL-based dose of allopurinol for at least one month and with a SU greater than or equal to 0.36mmol/L will be recruited.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with a history of intolerance to allopurinol and patients receiving azathioprine

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)
Allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomised allocation into the two groups in a 1:1 ratio will be made using a computer generated randomisation list. This list will be compiled prior to any randomisation and will stratify allocation based on site (Auckland/Christchurch) and arrange the allocation in permuted blocks
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Patients in the control will cross over to dose escalation after 12 months
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment outside Australia
Country [1] 3750 0
New Zealand
State/province [1] 3750 0
Auckland
Country [2] 3751 0
New Zealand
State/province [2] 3751 0
Christchurch

Funding & Sponsors
Funding source category [1] 267538 0
Government body
Name [1] 267538 0
Health Research Council of New Zealand
Address [1] 267538 0
PO Box 5541, Wellesley Street, Auckland 1141
Country [1] 267538 0
New Zealand
Primary sponsor type
Individual
Name
Lisa Stamp
Address
Department of Medicine
University of Otago, Christchurch
P.O.Box 4345
Christchurch 8011
Country
New Zealand
Secondary sponsor category [1] 266576 0
University
Name [1] 266576 0
University of Otago, Christchurch
Address [1] 266576 0
POBox 4345
Christchurch 8011
Country [1] 266576 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269493 0
Multiregional Ethics Committee
Ethics committee address [1] 269493 0
Ministry of Heath
P.O.Box 5013
Wellington 6145
Ethics committee country [1] 269493 0
New Zealand
Date submitted for ethics approval [1] 269493 0
01/07/2011
Approval date [1] 269493 0
15/09/2011
Ethics approval number [1] 269493 0
MEC/11/06/060

Summary
Brief summary
Gout is common in New Zealand, particularly in Maori and Pacific people. It is an extremely painful form of arthritis caused by uric acid crystals within joints. Repeated gout attacks cause joint damage. To prevent gout attacks, blood urate levels must be lowered to <0.36mmol/L. The most commonly used medication is allopurinol, which inhibits the production of urate. Current recommendations for allopurinol dose are based on kidney function. There is ample evidence that many patients fail to achieve adequate reduction in urate levels with the recommended dose. We have preliminary evidence that increasing the dose above recommended dose is safe and effective. We wish to undertake a clinical trial to confirm our preliminary findings, especially with respect to the safety of this approach. This study has the potential to provide a significant change in clinical practice and improve control of gout, thereby preventing joint damage and disability.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 32935 0
Prof Lisa Stamp
Address 32935 0
Department of Medicine
University of Otago, Christchurch
P.O.Box 4345
Christchurch 8014
Country 32935 0
New Zealand
Phone 32935 0
+6433640853
Fax 32935 0
Email 32935 0
lisa.stamp@cdhb.health.nz
Contact person for public queries
Name 16182 0
Prof Lisa Stamp
Address 16182 0
Department of Medicine
University of Otago, Christchurch
POBox 4345
Christchurch 8011
Country 16182 0
New Zealand
Phone 16182 0
+64-3-364-0953
Fax 16182 0
+64-3-364-0935
Email 16182 0
lisa.stamp@cdhb.govt.nz
Contact person for scientific queries
Name 7110 0
Prof Lisa Stamp
Address 7110 0
Department of Medicine
University of Otago, Christchurch
POBox 4345
Christchurch 8011
Country 7110 0
New Zealand
Phone 7110 0
+64-3-364-0953
Fax 7110 0
+64-3-364-0935
Email 7110 0
lisa.stamp@cdhb.govt.nz