None listed
Conditions
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.
Interventions
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
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
Sponsors
Lisa Stamp
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed