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Trial registered on ANZCTR


Registration number
ACTRN12618001179224
Ethics application status
Approved
Date submitted
5/07/2018
Date registered
17/07/2018
Date last updated
27/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Colchicine prophylaxis in gout patients commencing urate lowering therapy
Scientific title
Safety and efficacy study of colchicine prophylaxis in gout patients commencing urate lowering therapy
Secondary ID [1] 295353 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 308569 0
Condition category
Condition code
Musculoskeletal 307524 307524 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 307629 307629 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is colchicine 0.5mg as an oral capsule daily for six months. Adherence will be monitored by a drug tablet return at three month and six month study visits. Colchicine and allopurinol will be commenced together at the baseline visit.

All participants will receive allopurinol regardless of randomisation.
Intervention code [1] 301672 0
Treatment: Drugs
Comparator / control treatment
Placebo inert Calcium Lactate daily for six months as an identical oral capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 306500 0
The mean number of gout flares per month measured using a study specific questionnaire and self reported flare requiring treatment.
Timepoint [1] 306500 0
Questionnaire completed monthly for 12 months post enrolment.
Primary outcome [2] 306611 0
Adverse effects related to colchicine . Possible side effects relating to colchicine include skin rash, fever, diarrhoea, difficulty passing urine, muscle weakness or numbness, bleeding, and mouth ulcers. Adverse events will be recorded using a study specific questionnaire.
Timepoint [2] 306611 0
Questionnaire completed monthly for 6 months post enrolment.
Secondary outcome [1] 348815 0
Percentage of participants with flares at each month measured using a study specific questionnaire and by self reported flares requiring treatment.
Timepoint [1] 348815 0
Questionnaire completed monthly for 12 months post enrolment.
Secondary outcome [2] 349006 0
Time to first gout flare measured using a study specific questionnaire
Timepoint [2] 349006 0
Questionnaire completed monthly for 12 months post-enrolment.
Secondary outcome [3] 349007 0
Need for and dosage of rescue therapy for gout flares measured using study specific questionnaire.
Timepoint [3] 349007 0
Questionnaire completed monthly for 12 months post-enrolment.
Secondary outcome [4] 349008 0
Cost effectiveness : using the Otago Costs and Consequences Questionnaire (OCC-Q)
Timepoint [4] 349008 0
Questionnaire completed at enrolment, and month 6 and month 12 post enrolment.
Secondary outcome [5] 349009 0
Change in serum urate
Timepoint [5] 349009 0
Between baseline and 6 and 12 months post-enrolment
Secondary outcome [6] 349010 0
Change from baseline in subcutaneous tophus count measured using a study-specific assessment.
Timepoint [6] 349010 0
Between baseline and 6 and 12 months post-enrolment
Secondary outcome [7] 349011 0
Change from baseline in pain using 100mm visual analogue scale
Timepoint [7] 349011 0
Between baseline and 6 and 12 months post enrolment
Secondary outcome [8] 349012 0
Change from baseline in patient global assessment score using 100mm visual analogue scale
Timepoint [8] 349012 0
Between baseline and 6 and 12 months post-enrolment
Secondary outcome [9] 349013 0
Change from baseline in health related quality of life using the EQ-5D-3L
Timepoint [9] 349013 0
Between baseline and 6 and 12 months post-enrolment
Secondary outcome [10] 349014 0
Change from baseline in activity limitation as measured by the Health assessment questionnaire score
Timepoint [10] 349014 0
Between baseline and 6 and 12 months post-enrolment

Eligibility
Key inclusion criteria
*Gout according to the 2015 American College of Rheumatology and European League Against Rheumatism criteria
Serum urate >0.36mmol/
*At least one self-reported gout flare in last 6 months
*Fulfilling American College of Rheumatology criteria for urate lowering therapy with allopurinol (gout with greater than or equal to 2 flares in a year, tophi, chronic kidney disease greater than or equal to stage 2 (eGFR<90mls/min/1.73m2), or past kidney stones)
*Agreeable to starting allopurinol
*Ability to give informed consent
*Ability to communicate via telephone
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Contra-indication or previous intolerance to allopurinol
*Contra-indication or previous intolerance to colchicine
*Urate lowering therapy within 1 month of enrolment
*Stage 4 or 5 chronic kidney disease
*Concomitant azathioprine, cyclosporine, or other immunosuppression
*Unstable co-morbid health conditions (e.g stage 4 heart failure, recent myocardial infarction, advanced cancer)
*Dementia
*Unable to comply with study procedures
*Use of regular non steroidal anti inflammatory for other medical conditions.

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)
Study medication will be dispensed by blinded study coordinators using sequentially numbered medication packs. These packs will be manufactured and prepared by Optimus Health using the randomisation list prepared by the independent statistician. Medication bottles will be labelled with study number.

In the case of an individual patient emergency requiring un-blinding, the randomisation sequence will be held by an independent clinical nurse specialist in rheumatology at Christchurch Hospital and Auckland Hospital who will have no involvement with the study. Un-blinding may be requested by the principal investigator or a delegated alternative at each site in the unlikely event that clinical circumstances dictate that this is necessary.
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 on study site (Auckland/Christchurch) and will be arranged in permute blocks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
No interim efficacy or safety analyses are intended. All baseline demographic and clinical features will be summarized by randomized groups using means, medians, standard deviations ranges and frequencies and percentages as appropriate. No formal hypothesis testing will be undertaken on the baseline measurements. Primary and secondary efficacy endpoints will be compared between randomized groups using logistic regression, general linear models, generalized linear models and Cox proportional hazards regression dependent upon the form of the outcome variable. These models will include the baseline levels of the dependent variables as co-variates and stratum as covariates. Odds ratios, number needed treat and number needed to harm, mean differences and hazards ratios with 95% confidence intervals will be used to summarize relative efficacy of the randomized treatments. All analyses will be undertaken SPSS. All tests will be two-tailed and a 5% significance level maintained. Primary data analyses will be performed on the intention-to-treat population, all randomized participants. Secondary analysis will be based on the per-protocol basis which excludes participants with major protocol deviations. For those participants who withdraw or are lost to follow-up before six months the primary outcome (mean number of gout flares per month) will be calculated from their available data.
Exploratory analyses exploring differential effects of colchicine will be undertaken using baseline serum urate, presence or absence of tophi at baseline, baseline flare rate, allopurinol dose and adherence as sub-groups in the above models for the efficacy outcomes. These differential effects will be statistically tested by including the sub-group by randomized treatment interaction term in the models.
All adverse events and serious adverse events will be tabulated by system/organ class, severity and relatedness by randomized group as both frequency of event and percentage of participants experiencing the event. Key adverse events potentially related to colchicine treatment e.g. diarrhea may be compared between randomized groups using Chi-square or Fisher’s exact tests as appropriate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 10593 0
New Zealand
State/province [1] 10593 0
Canterbury
Country [2] 10618 0
New Zealand
State/province [2] 10618 0
Auckland

Funding & Sponsors
Funding source category [1] 299944 0
Government body
Name [1] 299944 0
Health Research Council
Address [1] 299944 0
PO Box 5541,
Wellesley Street,
Auckland 1141
Country [1] 299944 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
PO Box 4345
Christchurch 8014,
New Zealand
Country
New Zealand
Secondary sponsor category [1] 299321 0
None
Name [1] 299321 0
Address [1] 299321 0
Country [1] 299321 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300811 0
Health and Disability Ethics Committee of New Zealand
Ethics committee address [1] 300811 0
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 300811 0
New Zealand
Date submitted for ethics approval [1] 300811 0
23/07/2018
Approval date [1] 300811 0
27/08/2018
Ethics approval number [1] 300811 0
18/STH/156

Summary
Brief summary
This protocol describes a 12-month double blind placebo controlled randomised non-inferiority trial in people commencing allopurinol for gout. The study will recruit 200 people with gout commencing urate lowering therapy using start-low go-slow allopurinol dose escalation approach. Participants will be randomly assigned to prophylaxis with colchicine 0.5mg daily or placebo for six months followed by a further six months of follow-up. The primary efficacy endpoint will be difference in mean number of flares per month between 0 and 6 months between randomised groups. The primary safety outcome will be adverse events over the period of study treatment. Secondary endpoints will include difference in mean number of flares per month between 0 – 3 months and 6 - 12 months, percentage of patients with flare at each month, time to first flare, need for rescue therapy for gout flares, and cost effectiveness.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84890 0
Prof Lisa Stamp
Address 84890 0
Department of Medicine,
University of Otago Christchurch
PO Box 4345,
Christchurch 8140,
Country 84890 0
New Zealand
Phone 84890 0
+64 3 364 0253
Fax 84890 0
+64 3 364 0935
Email 84890 0
lisa.stamp@cdhb.health.nz
Contact person for public queries
Name 84891 0
Mrs Jill Drake
Address 84891 0
Department of Medicine,
University of Otago Christchurch
PO Box 4345,
Christchurch 8140,
Country 84891 0
New Zealand
Phone 84891 0
+64 3 3786088
Fax 84891 0
Email 84891 0
jill.drake@cdhb.health.nz
Contact person for scientific queries
Name 84892 0
Prof Lisa Stamp
Address 84892 0
Department of Medicine,
University of Otago Christchurch
PO Box 4345,
Christchurch 8140,
Country 84892 0
New Zealand
Phone 84892 0
+64 3 364 0253
Fax 84892 0
+64 3 364 0935
Email 84892 0
lisa.stamp@cdhb.health.nz

No information has been provided regarding IPD availability
Summary results
No Results