ANZCTR - Registration

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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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Gout

Condition category

Condition code

Inflammatory and Immune System

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]

Treatment: Drugs

Comparator / control treatment

No comparator.

Control group

Dose comparison

Outcomes

Primary outcome [1]

Serum urate

Timepoint [1]

At each month visit

Secondary outcome [1]

Number of gouty attacks during the study period.

Timepoint [1]

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?

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

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Canterbury

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Arthritis New Zealand

Address [1]

Level 2, 166 Featherston St
Wellington 6011
New Zealand

Country [1]

New Zealand

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Canterbury Medical Research Foundation

Address [2]

16 St Asaph Street
Christchurch 8014
New Zealand

Country [2]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Christchurch

Ethics committee address [1]

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

Approval date [1]

09/05/2005

Ethics approval number [1]

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

Prof Lisa Stamp

Address

Department of Medicine
University of Otago, Christchurch
POBox 4345
Christchurch 8014

Country

New Zealand

Phone

+64 3 364 0253

Fax

lisa.stamp@cdhb.health.nz

Contact person for public queries

Name

Lisa Stamp

Address

Department of Medicine
P.O.Box 4345
Christchurch

Country

New Zealand

Phone

+64 3 364 0253

Fax

lisa.stamp@cdhb.health.nz

Contact person for scientific queries

Name

Lisa Stamp

Address

Department of Medicine
P.O.Box 4345
Christchurch

Country

New Zealand

Phone

64-3-364-0953

Fax

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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Documents added automatically

No additional documents have been identified.

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