Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000247471
Ethics application status
Approved
Date submitted
3/05/2007
Date registered
8/05/2007
Date last updated
26/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Optimising the treatment of gout
Scientific title
A Study of the Effect of Probenecid on the Pharmacokinetics and Pharmacodynamics of Allopurinol at Steady-State in Patients with Gout
Secondary ID [1] 290215 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The effectiveness of the co-administration of allopurinol and probenecid in patients with gout 1786 0
Condition category
Condition code
Metabolic and Endocrine 1872 1872 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients already receiving allopurinol for at least one week will be co-administered (oral) probenecid starting at 500 mg/day. This dose will be increased (500 mg weekly to a maximum of 2g/ day) until plasma urate concentrations fall below 0.36mmol/L or are decreased by at least 20%, and no side effects have been experienced. Patients will have the following measured every 3-11 days, this being a period that approximates steady-state: plasma urate, plasma creatinine, urinary urate and urinary creatinine using standard biochemical analysis and plasma and urinary oxypurinol using validated methods.
During the study patients will be given prophylactic medication (e.g. NSAIDs or colchicine) to prevent acute attacks of gout in accordance with standard clinical practice.
Intervention code [1] 1735 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2660 0
To investigate the pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in patients with gout.
Timepoint [1] 2660 0
Plasma oxypurinol, probenecid and urate concentrations will be assessed and monitored at baseline and subsequently every 3-11 days until completion of the study.
Secondary outcome [1] 4515 0
1. To examine the impact of genetic variation in renal urate transporters on the response of patients to urate lowering medicines.
Timepoint [1] 4515 0
This will be assessed after completion of the study period.
Secondary outcome [2] 4516 0
2. To examine the effect of renal function on both the effectiveness of probenecid and the dose of allopurinol required to maintain appropriate concentrations of urate in plasma.
Timepoint [2] 4516 0
Plasma urate concentrations will be assessed at baseline and subsequently every 3-11 days until completion of the study.

Eligibility
Key inclusion criteria
Patients taking allopurinol for the indication of hyperuricaemia and/or gout.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A history of sensitivity to allopurinol or probenecid2. A history of nephrolithiasis3. Patients taking drugs likely to interfere with the pharmacokinetics of allopurinol or probenecid including: salicylates (high doses) 4. Drugs likely to interact with probenecid including: valaciclovir, acyclovir, famiciclovir, penciclovir, ganciclovir, zidovudine, methotrexate, lorazepam, midazolam, nitrazepam. Note: Drugs which may affect plasma urate concentrations need to be taken consistently throughout the study to avoid biasing the plasma urate concentrations.

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
1/06/2007
Actual
12/08/2008
Date of last participant enrolment
Anticipated
Actual
10/07/2009
Date of last data collection
Anticipated
Actual
11/09/2009
Sample size
Target
50
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 2019 0
Hospital
Name [1] 2019 0
Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital Sydney Ltd
Country [1] 2019 0
Australia
Primary sponsor type
Hospital
Name
Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital Sydney Ltd
Address
Department of Clinical Pharmacology and Toxicology, St Vincent's Hopsital, Darlinghurst 2010, Sydney
Country
Australia
Secondary sponsor category [1] 1829 0
None
Name [1] 1829 0
N/A
Address [1] 1829 0
Country [1] 1829 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3746 0
St Vincent’s Hospital
Ethics committee address [1] 3746 0
Ethics committee country [1] 3746 0
Australia
Date submitted for ethics approval [1] 3746 0
Approval date [1] 3746 0
30/01/2006
Ethics approval number [1] 3746 0
H06-141

Summary
Brief summary
Gout is an inflammatory condition caused by the deposition of urate crystals in tissues/joints. Allopurinol is a common and effective treatment to prevent gout. Probenecid, although less common used, is also effective, but may be less effective in patients with impaired renal function. In patients with tophaceous gout or those unresponsive to allopurinol/probenecid alone, the combination is sometimes prescribed. Studies in healthy subjects have shown that although the elimination of oxypurinol (active metabolite of allopurinol) is increased when probenecid is taken concurrently with allopurinol, the combination therapy has a greater therapeutic effect (decreased plasma urate concentrations). The relevance of these findings for gouty patients is unknown. Thus, this project will examine the interaction between allopurinol and probenecid in gouty patients and determine the therapeutic effect in patients with a range of renal function.
Trial website
Trial related presentations / publications
Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in healthy subjects. Stocker SL, Williams KM, McLachlan AJ, Graham GG, Day RO. Clin Pharmacokinet. 2008;47(2):111-8.
Public notes

Contacts
Principal investigator
Name 27838 0
Prof Richard Day
Address 27838 0
Clinical Pharmacology and Toxicology St Vincent's Hospital Victoria St Darlinghurst NSW 2010
Country 27838 0
Australia
Phone 27838 0
+61 2 83822331
Fax 27838 0
Email 27838 0
[email protected]
Contact person for public queries
Name 10924 0
Prof Richard Day
Address 10924 0
Clinical Pharmacology and Toxicology
St Vincent's Hospital
Victoria St
Darlinghurst NSW 2010
Country 10924 0
Australia
Phone 10924 0
+61 2 83822331
Fax 10924 0
Email 10924 0
[email protected]
Contact person for scientific queries
Name 1852 0
Prof Richard Day
Address 1852 0
Clinical Pharmacology and Toxicology
St Vincent's Hospital
Victoria St
Darlinghurst NSW 2010
Country 1852 0
Australia
Phone 1852 0
+61 2 83822331
Fax 1852 0
Email 1852 0
[email protected]

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.