Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000276550
Ethics application status
Approved
Date submitted
28/06/2006
Date registered
3/07/2006
Date last updated
19/09/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot study of high dose allopurinol in the management of gout:
Scientific title
A pilot study of high dose allopurinol in the treatment of gout:
Secondary ID [1] 287701 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 1251 0
Condition category
Condition code
Inflammatory and Immune System 1337 1337 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PARTICIPANTS will be classified into one of the following groups:
1. Participants who are on the recommended dose of allopurinol and have a serum urate <0.35mmol/l will be classified as responders to standard therapy. They will be seen three monthly.

2. Participants who are on the recommended dose of allopurinol who have a serum urate > 0.35mmol/l and a plasma oxypurinol 80-100micromol/L will be deemed as compliant but non-responsive to standard therapy. These participants will be treated at the discretion of the investigator.
3 Participants who are on the recommended dose with plasma urate >0.35mmol/l and plasma oxypurinol <30micromol/L will be deemed non-compliant non-responders. They will be educated about the need for treatment and encouraged to become compliant. If they become compliant and they still have low plasma oxypurinol levels and high serum urate they will be given the option of entering the dose escalation group (see 4).

4. Participants on the recommended dose of allopurinol with a serum urate >0.35mmol/l and plasma oxypurinol 30-80micromol/L will have the dose of allopurinol increased by 100mg/day every month until either:

(a) Plasma urate <0.35mmol/l AND/OR
(b) Plasma oxypurinol 80-100micromol/l AND/OR
(c) Allopurinol dose 900mg/day (or at a lower dose at the discretion of the investigator) AND/OR
(d) Adverse event ascribed to allopurinol requiring cessation of allopurinol (e.g. allopurinol hypersensitivity syndrome, rash, significant liver function or blood count abnormalities, vomiting)

Group 4 from above form the basis of this study: those that are compliant but not responding to the recommended allopurinol dose. It is anticipated that of the 100 patients followed between 20 and 30 will be of this type.
During the course of the study, management of acute attacks of gout will be at the discretion of the investigator in accordance with standard clinical care (e.g. NSAID, colchicine or oral/intra-articular steroid). Allopurinol will not be discontinued during the acute attack.

Allopurinol is given orally.

participant will be seen 1-3 monthly for 12 months will
Intervention code [1] 1176 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Dose comparison

Outcomes
Primary outcome [1] 1823 0
Serum urate
Timepoint [1] 1823 0
At each month visit
Secondary outcome [1] 3190 0
Number of gouty attacks during the study period.
Timepoint [1] 3190 0
12 months of study

Eligibility
Key inclusion criteria
1. Patients fulfil the diagnostic criteria of gout (Wallace, Robinson et al. 1977) which are as follows Clinical diagnosis of gout requires either A, B, or C to be metA. The presence of characteristic urate crystals in the joint fluidB. A tophus proved to contain urate crystals by chemical means or polarised light microscopyC. The presence of 6 of the following 12 clinical laboratory, and x-ray phenomenaI. Maximum inflammation developed within one dayII. More than one attack of acute arthritisIII. Attack of monoarthritisIV. Redness observed over the affected joint(s)V. First metatarsophalangeal joint painful or swollenVI. Unilateral first metatarsophalangeal joint attackVII. Unilateral attack involving tarsal jointVIII. Suspected tophusIX. HyperuricaemiaX. Asymmetric swelling within a joint XI. Subcortical cysts without erosionsXII. Negative culture of joint fluid for microorganisms during attack of joint inflammation. 2. Subjects are willing and able to participate in the study and from whom written informed consent has been obtained.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of adverse effects with use of allopurinol.2. Patients currently taking azathioprine3. Patients with a solid organ transplant (eg kidney, liver or heart transplant)4. Presence of chronic infection or other severe concomitant medical illness or psychiatric disease.5. Pregnant or breast-feeding females and female subjects of child bearing age who are not practising medically approved methods of contraception.6. HIV positive patients.7. History of drug abuse that would interfere with the ability to comply with the study protocol.8. Patients with active, concomitant malignancies.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2006
Actual
9/03/2006
Date of last participant enrolment
Anticipated
Actual
12/08/2008
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
90
Recruitment outside Australia
Country [1] 371 0
New Zealand
State/province [1] 371 0
Canterbury

Funding & Sponsors
Funding source category [1] 1462 0
Charities/Societies/Foundations
Name [1] 1462 0
Arthritis New Zealand
Country [1] 1462 0
New Zealand
Funding source category [2] 292255 0
Charities/Societies/Foundations
Name [2] 292255 0
Canterbury Medical Research Foundation
Country [2] 292255 0
New Zealand
Primary sponsor type
Individual
Name
Lisa Stamp
Address
Department of Medicine
University of Otago, Christchurch
POBox 4345
Christchurch 8014
New Zealand
Country
New Zealand
Secondary sponsor category [1] 1291 0
None
Name [1] 1291 0
Address [1] 1291 0
Country [1] 1291 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2842 0
Christchurch
Ethics committee address [1] 2842 0
Ethics committee country [1] 2842 0
New Zealand
Date submitted for ethics approval [1] 2842 0
Approval date [1] 2842 0
09/05/2005
Ethics approval number [1] 2842 0
URB/05/03/026

Summary
Brief summary
Gout is a common and challenging problem in New Zealand. It is an extremely painful form of arthritis with higher rates in the New Zealand community compared to the rest of the world. Gout is caused by uric acid crystals within joints. These crystals lead to inflammation and with repeated attacks joint damage can occur resulting in significant disability. Uric acid crystals enter the joints when blood uric acid levels are high. In order to prevent gout and joint damage, blood uric acid levels must be lowered. The most commonly used medication is allopurinol. Allopurinol is metabolised to oxypurinol, which inhibits one of the enzymes involved in the formation of uric acid. Oxypurinol can be measured within the blood and there is a published therapeutic range. There are currently guidelines for the dose of allopurinol based on kidney function. Many patients do not have an adequate reduction in blood uric acid and attacks of gout with the recommended dose of allopurinol. In those that fail to respond, the dose of allopurinol is often increased to levels above the recommended dose. However, there is only anecdotal evidence about whether this increase in dose is effective. We wish to investigate whether increasing the dose of allopurinol, in those that fail to respond to the recommended dose, results in any further reduction in blood uric acid levels and fewer attacks of gout. Adverse events will be closely monitored. We will use the oxypurinol level to help guide the dose increase. In the first instance we aim to do a pilot study with the intention of a larger, multi-centre study should the results suggest a clinical benefit.
Trial website
Trial related presentations / publications
1. LK Stamp, JL O’Donnell, M Zhang, J James, C Frampton, ML Barclay, PT Chapman. Using allopurinol above the dose based on creatinine clearance is effective and safe in chronic gout, including in those with renal impairment. Arthritis Rheum 2011;63(2);412-421.
2. LK Stamp, ML Barclay, JL O’Donnell, M Zhang, J Drake, C Frampton, and PT Chapman. Relationship between serum urate and plasma oxypurinol – is there a target plasma oxypurinol concentration to achieve serum urate <0.36mmol/L? Clin Pharm Ther 2011; 90(3):392-8.
Public notes

Contacts
Principal investigator
Name 36357 0
Prof Lisa Stamp
Address 36357 0
Department of Medicine
University of Otago, Christchurch
POBox 4345
Christchurch 8014
Country 36357 0
New Zealand
Phone 36357 0
+64 3 364 0253
Fax 36357 0
Email 36357 0
lisa.stamp@cdhb.health.nz
Contact person for public queries
Name 10365 0
Prof Lisa Stamp
Address 10365 0
Department of Medicine
P.O.Box 4345
Christchurch
Country 10365 0
New Zealand
Phone 10365 0
+64 3 364 0253
Fax 10365 0
Email 10365 0
lisa.stamp@cdhb.health.nz
Contact person for scientific queries
Name 1293 0
Prof Lisa Stamp
Address 1293 0
Department of Medicine
P.O.Box 4345
Christchurch
Country 1293 0
New Zealand
Phone 1293 0
64-3-364-0953
Fax 1293 0
Email 1293 0
lisa.stamp@cdhb.health.nz

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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