Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001279718
Ethics application status
Approved
Date submitted
31/08/2022
Date registered
29/09/2022
Date last updated
27/01/2023
Date data sharing statement initially provided
29/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Allopurinol prescribing for gout management in Aotearoa New Zealand
Scientific title
Easing the way to achieving target serum urate in people with gout: a non-inferiority strategy trial using an allopurinol dosing model. (The Easy-Allo study)
Secondary ID [1] 307846 0
HRC 22/574
Universal Trial Number (UTN)
U1111-1281-9855
Trial acronym
The Easy-Allo study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 327458 0
Condition category
Condition code
Musculoskeletal 324583 324583 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Allopurinol dose escalation to a maximum of 900mg will be based on a monthly serum urate and phone contact with the study coordinator. The dose will be increased until serum urate has been <0.36mmol/l for three, monthly consecutive visits. Starting dose of allopurinol will be 50mg daily in those with eGFR<60mls/min and 100mg daily in those with eGFR great than or equal 60mls/min. For all participants allopurinol dose will be increased monthly by 50 or 100mg per day as determined by eGFR. Adherence will be assessed by pill count. Participants will continue allopurinol for the entire 36 months. Allopurinol will be in the form of an oral tablet.
Intervention code [1] 324311 0
Treatment: Drugs
Comparator / control treatment
The predicted dose of oral allopurinol will be based on the model-derived dosing guideline. The predicted dose is based on patient weight, serum urate at study entry and concomitant use of diuretic and has been designed for this study. Participants will be provided with a written plan and prescriptions for allopurinol at baseline and then every three months. The participants will be instructed to increase the allopurinol at monthly intervals until the predicted dose or a maximum of 900mg daily has been reached. Participants will continue allopurinol for the entire 36 months. Adherence will be assessed by pill count.
Control group
Active

Outcomes
Primary outcome [1] 332402 0
The proportion of participants with serum urate <0.36mmol/l
Timepoint [1] 332402 0
Month 12 post-intervention commencement
Secondary outcome [1] 413357 0
Number of self reported gout flares requiring treatment from a study-specific questionnaire
Timepoint [1] 413357 0
Between baseline and month 12 post-intervention commencement measured three monthly
Secondary outcome [2] 413358 0
Allopurinol related treatment emergent adverse events from a study-specific questionnaire
Timepoint [2] 413358 0
From baseline to month 12 post-intervention commencement - measured three monthly
Secondary outcome [3] 413359 0
Difference in the number of interactions with the health professionals between randomised groups from a study-specific questionnaire
Timepoint [3] 413359 0
From baseline to month 12 post-intervention commencement - measured three monthly
Secondary outcome [4] 413600 0
Difference in average time taken for each interaction with the health professionals between randomised groups using a study specific questionnaire
Timepoint [4] 413600 0
Between baseline and month 12 post-intervention commencement - measured three monthly
Secondary outcome [5] 413601 0
Change in serum urate
Timepoint [5] 413601 0
Over 12 months post commencement of intervention measured three monthly
Secondary outcome [6] 413602 0
Change in subcutaneous tophus count assessed by manual count by study coordinators
Timepoint [6] 413602 0
Over 12 months post commencement of intervention measured three monthly
Secondary outcome [7] 413603 0
Change in pain using 100mm visual analogue score
Timepoint [7] 413603 0
Over 12 months post commencement of intervention - measured three monthly
Secondary outcome [8] 413604 0
Change patient global assessment score using 100mm visual analogue measured three monthly
Timepoint [8] 413604 0
Over 12 months post commencement of intervention measured three monthly
Secondary outcome [9] 413605 0
Change in health-related quality of life using the EQ-5D-5L
Timepoint [9] 413605 0
Over 12 months post commencement of intervention measured three monthly
Secondary outcome [10] 413606 0
Change in activity limitation as measured by the Health Assessment Questionnaire-II
Timepoint [10] 413606 0
Over 12 months post commencement of intervention measured three monthly
Secondary outcome [11] 413607 0
Proportion of participants who have at least one self reported gout flare using a study specific questionnaire
Timepoint [11] 413607 0
From baseline to month 12 post intervention commencement measured three monthly
Secondary outcome [12] 413608 0
Proportion of participants achieving serum urate <0.36mmol/l
Timepoint [12] 413608 0
At month 6 post intervention commencement
Secondary outcome [13] 413609 0
Proportion of participants taking any allopurinol from a study-specific questionnaire
Timepoint [13] 413609 0
Over 12 months post commencement of intervention
Secondary outcome [14] 413610 0
Proportion of participants taking the prescribed allopurinol dose
Timepoint [14] 413610 0
Over 12 months post commencement of intervention
Secondary outcome [15] 413611 0
Adherence to allopurinol as assessed by pill counts
Timepoint [15] 413611 0
Over 12 months post commencement of intervention
Secondary outcome [16] 413612 0
For those taking allopurinol the mean allopurinol dose from a study-specific questionnaire
Timepoint [16] 413612 0
Over 12 months post commencement of intervention
Secondary outcome [17] 413613 0
Proportion of people fulfilling the provisional gout remission criteria ( this is a composite endpoint including the domains of pain, patient global assessment, tophus, gout flares and serum urate
Timepoint [17] 413613 0
Over 12 months post commencement of intervention

Eligibility
Key inclusion criteria
1. Age over 18 years
2. Gout according to the 2015 ACR/EULAR criteria
3. Serum urate greater than or equal to 0.36mmol/l (6mg/dl) AND
- not taking allopurinol, but starting urate-lowering therapy strongly recommended in the 2020 ACR gout management guidelines (i.e. any of the following: greater than or equal to 2 gout flares/year, greater than or equal to 1 subcutaneous tophi, radiographic damage due to gout) OR
- already taking allopurinol for gout at lower than predicted dose OR
- already taking allopurinol but not regularly
4. Agreeable to starting or continuing allopurinol
5. Ability to give informed consent
6. Ability to communicate via telephone
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe kidney disease with estimated glomerular filtration rate (eGFR) <30ml/min/1.73m2
2. Contra-indication or previous intolerance to allopurinol
3. Concomitant azathioprine, due to interactions with allopurinol
4. HLA-B*5801 positive in high allele frequency populations (South East Asian and African), due to high risk of allopurinol hypersensitivity syndrome
5. Female of childbearing age not on contraception
5. Unstable co-morbid health conditions (e.g. NYHA stage 4 heart failure, recent myocardial infarction, advanced cancer)
6. Dementia

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation list will be generated by the independent study statistician using a computer-generated list. Randomisation will be stratified according to ethnicity (Maori, Pacific peoples, non-Maori/non-Pacific peoples) and by those starting or continuing allopurinol and will be arranged in permuted blocks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Non-inferiority
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on our previous data, ~80% participants achieved target serum urate <0.36mmol/l . A sample size of 190 per group is required to detect 15% non-inferiority (<65% achieve target urate), if the true serum urate target rates are the same in both groups, with 90% power. The 15% non-inferiority margin is well accepted in rheumatology randomised controlled trials,. The primary analysis of non-inferiority will be conducted using the per protocol sample of randomised participants, i.e. excluding those participants with major protocol violations. A sensitivity analysis will be undertaken using the intention-to-treat sample. For equal explanatory, power we would need 380 participants per ethnicity group (n=1140 overall), which is impractical in the Aotearoa/New Zealand setting and beyond the funding of an HRC Programme Grant or indeed any other national funding. The primary analysis of non-inferiority will be conducted using the per protocol sample of randomised patients, i.e. excluding those participants with major protocol violations. A sensitivity analysis will be undertaken using the intention to treat sample.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
6/02/2023
Actual
Date of last participant enrolment
Anticipated
3/03/2025
Actual
Date of last data collection
Anticipated
31/03/2028
Actual
Sample size
Target
380
Accrual to date
0
Final
Recruitment outside Australia
Country [1] 24977 0
New Zealand
State/province [1] 24977 0
Auckland
Country [2] 24978 0
New Zealand
State/province [2] 24978 0
Canterbury

Funding & Sponsors
Funding source category [1] 312121 0
Government body
Name [1] 312121 0
Health research Council of New Zealand
Country [1] 312121 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
P.O. Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 313643 0
None
Name [1] 313643 0
Address [1] 313643 0
Country [1] 313643 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311520 0
New Zealand Health and Disability Ethics Committee
Ethics committee address [1] 311520 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 311520 0
New Zealand
Date submitted for ethics approval [1] 311520 0
23/09/2022
Approval date [1] 311520 0
10/10/2022
Ethics approval number [1] 311520 0
2022 FULL 13478

Summary
Brief summary
Gout is particularly prevalent in Aotearoa/NZ, with 13.8% of Maori men, 22.5% of
Pacific men, and 6.9% of NZ European men affected. Effective management requires
lowering the blood urate level to a treatment target, usually with a medication called
allopurinol. There are important inequities based on ethnicity in allopurinol prescribing
in Aotearoa. The current best practice treatment strategy is time consuming and
difficult to implement. An easier way to use allopurinol is required, especially since gout
disproportionately affects middle-age men who are frequently working and are not able
to take time off work or afford the costs involved with the current strategy. The aim of
this Programme is to determine whether a protocol-driven allopurinol dose escalation
strategy based on the dose predicted to achieve target urate is as effective as the
current best practice intensive treat-to-target strategy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121386 0
Prof Lisa Stamp
Address 121386 0
Department of Medicine
University of Otago, Christchurch
P. O. Box 4345
Christchurch 8011
Country 121386 0
New Zealand
Phone 121386 0
+64 3 364 0253
Fax 121386 0
Email 121386 0
lisa.stamp@cdhb.health.nz
Contact person for public queries
Name 121387 0
Ms Jill Drake
Address 121387 0
Department of Medicine
University of Otago, Christchurch
P. O. Box 4345
Christchurch 8011
Country 121387 0
New Zealand
Phone 121387 0
+64 3 378 6088
Fax 121387 0
Email 121387 0
jill.drake@cdhb.health.nz
Contact person for scientific queries
Name 121388 0
Prof Lisa Stamp
Address 121388 0
Department of Medicine
University of Otago, Christchurch
P. O. Box 4345
Christchurch 8011
Country 121388 0
New Zealand
Phone 121388 0
+64 3 364 0253
Fax 121388 0
Email 121388 0
lisa.stamp@cdhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will not be deposited in an external registry or shared for IPD analysis. Analyzed data may be made availabe upon reasonable request following review by the trial steering committee with appropriate acknowledgements. This approach is consistent with Indigenous data sovereignty principles.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17030Study protocol  lisa.stamp@cdhb.health.nz We are planning to publish the protocol and will a... [More Details]



Results publications and other study-related documents

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