Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000743965
Ethics application status
Approved
Date submitted
13/07/2011
Date registered
15/07/2011
Date last updated
26/09/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Optimising allopurinol therapy in the treatment of gout.
Scientific title
Understanding the dose-response relationship of allopurinol in patients with gout.
Secondary ID [1] 262615 0
Nil
Universal Trial Number (UTN)
U1111-1122-8998
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 268312 0
Condition category
Condition code
Inflammatory and Immune System 268440 268440 0 0
Other inflammatory or immune system disorders
Musculoskeletal 268464 268464 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who have gout and not yet taking allopurinol will be recruited. They will then start with a low dose of allopurinol taken by oral tablet. This low dose will be 50 mg/day (for low renal function) or 100 mg/day (for normal renal function). Patients will take allopurinol for at least 1-2 weeks, being sufficient time to reach steady state concentrations (depending on renal function). Patients will then have the following measured: plasma and urinary urate and creatinine concentrations using standard biochemical analyses and plasma oxypurinol concentrations using a validated method. Based on the efficacy of the dose of allopurinol in lowering plasma urate concentrations and at the discretion of the consultant rheumatologist, the rate of the dose increase and the size of the dose increase will rise. Two weeks after each dose increase, the above mentioned analytes will again be measured. This intervention will continue until the plasma urate concentrations drop to 0.30 mg/L.
Intervention code [1] 266962 0
Treatment: Drugs
Comparator / control treatment
Participants with similar renal functions will start with the same dose regime (50 mg/day for low renal function and 100 mg/day for normal renal function). Dose increases and the rate of increase will be dependent on the efficacy of particular doses in lowering plasma urate concentrations.
Control group
Active

Outcomes
Primary outcome [1] 269196 0
To understand the dose-response relationship of allopurinol.
Timepoint [1] 269196 0
Plasma urate, creatinine and oxypurinol concentrations will be monitored after each dose escalation until the close of the study.
Primary outcome [2] 269197 0
To achieve plasma urate concentrations lower than 0.30 mmol/L in patients with gout.
Timepoint [2] 269197 0
Allopurinol will be titrated upwards in patients with gout until plasma urate concentrations are lower than 0.30 mmol/L.
Secondary outcome [1] 279101 0
Determine what factors (dose, oxypurinol concentration, creatinine clearance, baseline plasma urate concentration) affect plasma urate concentrations achieved during treatment of allopurinol.
Timepoint [1] 279101 0
Factors that affect plasma urate concentrations of urate during allopurinol treatment will be determined after patients have reached plasma urate concentrations lower than 0.30 mmol/L.

Eligibility
Key inclusion criteria
Suffer from clinically diagnosed gout and commencing allopurinol therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Poor venous access for venepuncture.

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
Other
Other design features
Participants start to receive different doses of the intervention based on their renal function. The rate at which the dose is increased and the size of the dose increase is based on their response to the treatment. This response is measured by plasma urate concentrations.
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/06/2008
Actual
13/11/2008
Date of last participant enrolment
Anticipated
Actual
20/07/2010
Date of last data collection
Anticipated
Actual
9/08/2010
Sample size
Target
30
Accrual to date
Final
37
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 267445 0
Government body
Name [1] 267445 0
National Health and Medical Research Council Safety Grant
Country [1] 267445 0
Australia
Funding source category [2] 267446 0
Charities/Societies/Foundations
Name [2] 267446 0
Lexy Davies Bequest
Country [2] 267446 0
Australia
Primary sponsor type
Individual
Name
Richard Day
Address
Department of Clinical Pharmacology & Toxicology
Level 2 Xavier Building,
St Vincent's Hospital, Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 266477 0
None
Name [1] 266477 0
Address [1] 266477 0
Country [1] 266477 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269404 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 269404 0
Research Office
Level 6 deLacy Building,
St Vincent's Hospital, Victoria St
Darlinghurst NSW 2010
Ethics committee country [1] 269404 0
Australia
Date submitted for ethics approval [1] 269404 0
Approval date [1] 269404 0
31/10/2006
Ethics approval number [1] 269404 0
H06/107, 08/172

Summary
Brief summary
Gout is the most common inflammatory disease in the western hemisphere where its incidence seems to be rising. Allopurinol is a widely used and effective treatment for gout. It is used to lower plasma urate concentrations in the body, which in-turn prevents acute gout attacks. It's use, however, has been shown to be sub-optimal. Patients are not reaching target plasma urate concentrations recommended by treatment guidelines due to low dosing of allopurinol. Thus this project aims to understand the dose-response relationship of allopurinol and optimise the dose for patients, such that patients reach target plasma urate concentrations.
Trial website
Trial related presentations / publications
Stocker SS et al. (2012). The pharmacokinetics of oxypurinol in people with gout. Br J Clin Pharmacol 74 (3): 477-489.
Kannangra DRW et al. (2012). Fractional clearance of urate: validation of measurement in spot-urine samples in healthy subjects and gouty patients. Arth Res Ther 14: R189
Graham GG et al. (2013). Understanding the dose-response relationship of allopurinol: predicting the optimal dose. Br J Clin Pharmacol 76: 932-8.
Public notes

Contacts
Principal investigator
Name 32867 0
Prof Richard Day
Address 32867 0
Department of Clinical Pharmacology & Toxicology Level 2 Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst NSW 2010
Country 32867 0
Australia
Phone 32867 0
+61 2 8382 2304
Fax 32867 0
Email 32867 0
r.day@unsw.edu.au
Contact person for public queries
Name 16114 0
Prof Richard Day
Address 16114 0
Department of Clinical Pharmacology & Toxicology
Level 2 Xavier Building,
St Vincent's Hospital, Victoria St
Darlinghurst NSW 2010
Country 16114 0
Australia
Phone 16114 0
+61 2 8382 2304
Fax 16114 0
+61 2 8382 2724
Email 16114 0
r.day@unsw.edu.au
Contact person for scientific queries
Name 7042 0
Prof Richard Day
Address 7042 0
Department of Clinical Pharmacology & Toxicology
Level 2 Xavier Building,
St Vincent's Hospital, Victoria St
Darlinghurst NSW 2010
Country 7042 0
Australia
Phone 7042 0
+61 2 8382 2304
Fax 7042 0
+61 2 8382 2724
Email 7042 0
r.day@unsw.edu.au

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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