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Trial registered on ANZCTR


Registration number
ACTRN12609000529246
Ethics application status
Approved
Date submitted
25/06/2009
Date registered
2/07/2009
Date last updated
16/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Interaction between frusemide and allopurinol drug treatments in patients with gout
Scientific title
The effect of co-administration of frusemide with allopurinol on serum urate and plasma oxypurinol concentrations in patients with gout.
Secondary ID [1] 284342 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
gout 237061 0
Condition category
Condition code
Musculoskeletal 237380 237380 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: A pharmacokinetic study in ten patients with gout receiving stable dose allopurinol for at least one month will be undertaken (Group 1). Patients will be given a single oral dose of frusemide 40mg on day 2 of the study. PAtients will continue to take their usual allopurinol dose throughout the study. The dose of allopurinol will be determined by the treating physician and will therefore differ between patients.
On day one patients will take allopurinol only. Bloods will be taken at baseline, 0.5, 1, 2, 4 and 24 hours. On day two patients will be given 40mg frusemide orally in addition to their allopurinol and bloods will be taken at baseline, 0.5, 1, 2, 4, 24 and 48 hours. Serum uric acid, plasma oxypurinol and allopurinol will be assessed.
Group 2: 25 patients on allopurinol receiving concomitant frusemide with stable dose of both drugs for at least one month will be recruited. The dose of allopruinol and fursemide will be determined by the treating physician and will differ between patietns. Age, sex, creatinine clearance (CrCL) matched patients receiving allopurinol only will be recruited on a one-to-one ratio. Patients will be seen on one occasion only and assessed for serum uric acid and creatinine concentrations, plasma allopurinol and oxypurinol concentrations and urine urate and creatinine concentrations.
Group 3: 25 patients receiving stable dose allopurinol in which oral frusemide is commenced for a given clinical indication will be recruited. The dose and duration of of treatment with frusemide will be at the discretion of the treating clinician. Age, sex and CrCL matched patients receiving allopurinol only will be recruited on a one-one ratio. Cases will be seen at baseline, after 1 week and after 1 month on frusemide. Controls will be seen at matched time points. Patients will be assessed for serum uric acid and creatinine concentrations, plasma allopurinol and oxypurinol concentrations and urine urate and creatinine concentrations
Group4: 15 patients receiving less than or equal to 80mg frusemide in combination with allopurinol will have frusemide discontinued. Patients will be assessed at baseline and at day 7 for serum urate and creatinine, plasma oxypurinol and allopurinol, urine urate and creatinine. If patients remain stable frusemide may be discontinued for longer, if required for hypertension an alternative agent may be substituted.
for all groups the dose of allopruinol will be at the discretion of the treating physician for the management of gout.
Intervention code [1] 236779 0
Treatment: Drugs
Comparator / control treatment
Group 1: patients will act as their own controls on day one no frusemide given and on day 2 frusemide given
Group 2: is a case controlled group with no treatment given
Group 3: Frusemide will be commenced by the treating physician
Group 4: Frusemide stopped by treating physician
Control group
Active

Outcomes
Primary outcome [1] 238214 0
A change in serum urate concentration. Assessed using blood test
Timepoint [1] 238214 0
At each patient visit
Group one: baseline, 0.5, 1 2,4,24 an 48 hours
group 2: one visit ony
Group 3: at baseline, week 1 and week 4
Group 4: Baseline week 1 and week 4
Primary outcome [2] 238240 0
A change in plasma oxypurinol/allopurinol concentration. Assessed using blood test
Timepoint [2] 238240 0
At each patient visit
Group one: baseline, 0.5, 1 2,4,24 an 48 hours
group 2: one visit ony
Group 3: at baseline, week 1 and week 4
Group 4: Baseline week 1 and week 4
Primary outcome [3] 238241 0
A change in urine urate excretionconcentration. Assessed using urine test
Timepoint [3] 238241 0
Group one: baseline, 0.5, 1 2,4,24 an 48 hours
group 2: one visit ony
Group 3: at baseline, week 1 and week 4
Group 4: Baseline week 1 and week 4
Secondary outcome [1] 244573 0
Nil
Timepoint [1] 244573 0
Nil

Eligibility
Key inclusion criteria
Gout as defined by American College of Rheumatology Classification Criteria and on stable dose of allopurinol for at least one month
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Stopping or starting frusemide inappropriate, chronic infection or other severe medical illnesses, active malignancies, psychiatric illness

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)
Patients with gout as defined by American College of Rheumatology Classification criteria will be recruited. Patients starting (group3) and stopping (group4) frusemide will be recuited on the basis of starting/stopping frusemide by the treating physician.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Patients will be assigned depending on whether theya re starting or stopping frusemide. This decision will be made by their treating physician.
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/07/2009
Actual
27/07/2009
Date of last participant enrolment
Anticipated
Actual
5/03/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
125
Accrual to date
Final
125
Recruitment outside Australia
Country [1] 1843 0
New Zealand
State/province [1] 1843 0
Christchurch

Funding & Sponsors
Funding source category [1] 237208 0
Self funded/Unfunded
Name [1] 237208 0
Country [1] 237208 0
New Zealand
Primary sponsor type
Individual
Name
Lisa Stamp
Address
Department of Medicine
POBox 4345
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 4701 0
None
Name [1] 4701 0
Address [1] 4701 0
Country [1] 4701 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239296 0
Upper South A Regional Ethics Committee
Ethics committee address [1] 239296 0
Ministry of Health
P.O Box 3877
Christchurch 8140
Ethics committee country [1] 239296 0
New Zealand
Date submitted for ethics approval [1] 239296 0
Approval date [1] 239296 0
04/06/2009
Ethics approval number [1] 239296 0
URA/09/05/033

Summary
Brief summary
Gout is a common and challenging problem in New Zealand. It is an extremely painful form of arthritis with high rates in the New Zealand. Gout is caused by uric acid crystals within joints. Uric acid crystals enter the joints when blood uric acid levels are high. Gout is also associated with a number of other medical conditions including high blood pressure. One of the common treatments for high blood pressure, frusemide, a diuretic, increases blood uric acid levels. In order to prevent gout, blood uric acid levels must be lowered. The most commonly used medication is allopurinol which is metabolised to oxypurinol and inhibits an enzyme involved in the formation of uric acid. Previous studies in healthy volunteers have shown that there is an interaction between frusemide and allopurinol such that patients receiving both drugs have higher blood uric acid levels and higher oxypurinol levels. Previous workers have suggested that this makes allopurinol more effective. However, our experience in patients with gout is that the combination of allopurinol and frusemide makes gout more difficult to control. We therefore recommend cessation of frusemide where possible. However there is currently no data on the benefits of such an approach. The interaction between frusemide and allopurinol will be investigated in this study.
Trial website
Trial related presentations / publications
LK Stamp, ML Barclay, JL O’Donnell, M Zhang, J Drake, C Frampton, and PT Chapman. Frusemide increases plasma oxypurinol without lowering serum urate – a complex drug interaction: implications for clinical practice. Rheumatology 2012;51: 1670-76.
Public notes

Contacts
Principal investigator
Name 29769 0
Prof Lisa Stamp
Address 29769 0
Department of Medicine
University of Otago, Christchurch
POBox 4345
Christchurch
Country 29769 0
New Zealand
Phone 29769 0
+6433640253
Fax 29769 0
Email 29769 0
[email protected]
Contact person for public queries
Name 13016 0
Lisa Stamp
Address 13016 0
University of Otago
P.O Box 4345
Christchurch 8140
Country 13016 0
New Zealand
Phone 13016 0
+64 3 3640953
Fax 13016 0
Email 13016 0
[email protected]
Contact person for scientific queries
Name 3944 0
Lisa Stamp
Address 3944 0
University of Otago
P.O Box 4345
Christchurch 8140
Country 3944 0
New Zealand
Phone 3944 0
+64 3 3640953
Fax 3944 0
Email 3944 0
[email protected]

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