None listed
Conditions
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.
Interventions
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 base
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.
Sponsors
Lisa Stamp
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Gout as defined by American College of Rheumatology Classification Criteria and on stable dose of allopurinol for at least one month
Exclusion criteria
Stopping or starting frusemide inappropriate, chronic infection or other severe medical illnesses, active malignancies, psychiatric illness
Outcome results
None listed