Tight Control of Gouty Arthritis Compared to Usual Care

Study Overview
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Brief Summary
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Gout is caused by a reaction to urate crystals that results in attacks of severe joint pain. Medicines that lower urate levels can prevent gout flares, however it takes time for this benefit to be felt, and paradoxically starting treatment with large doses of urate lowering treatment risks provoking attacks of gout. Medical guidelines disagree on the best way to overcome these challenges with many recommending medicine dose adjustment based on regular urate testing but a general practice guideline suggesting more simply increasing the medicine dose in those patients that continue to suffer flares. In reality most patients are not treated at all, and many of those that are treated never receive an effective dose of treatment. We have developed a supported self-management approach to gout in which patients monitor their own urate levels using a finger prick test, and then receive advice on adjusting their treatment dose to achieve target urate levels through a smartphone app (Gout SMART). A trial of this approach has shown that it results in much better control of urate levels after 6 months than usual care, and suggests that it also leads to fewer flares. We would now like to confirm that this approach is effective in reducing flares of gout over 2 years by randomising patients to either treatment-to-target urate using our self-monitoring approach, or to treatment guided by symptoms only.

Detailed Description
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A total of approximately 240 participants will be recruited. We anticipate that most participants will be identified following referral to rheumatology outpatient or on-call services in National Health Service (NHS) Lothian, or through NHS Lothian's gout liaison service. Additional patients may indicate their willingness to participate directly in response to study advertisements. Based on baseline renal function and flare frequency, an individual treatment plan will be drawn up for all participants which will set a ceiling on the maximum dose of allopurinol to be used within the trial and determine the need for flare prophylaxis with colchicine. Participants will be randomized to the intervention group in a 1:1 ratio, with stratification by the need for use of flare prophylaxis. All participants will have a smart phone application (GoutSMART) uploaded to their smart phones. Treat-to-flare participants will have a limited version of the GoutSMART application installed which includes background information about gout and provides a means for participants to maintain diaries of gout flares and quality of life. Subjects in the treat-to-flare arm of the study will have treatment escalation decisions made by their GPs. Subjects in the treat-to-target arm will be taught to self-test serum urate using a BeneCheck Plus hand held device and provided with test strips. A full version of the GoutSMART application will be installed with the features mentioned above but also the facility to record a urate diary. Participants will be prompted to check their serum urate and enter the results into the GoutSMART application. Participants reporting a urate level >0.3mmol/l will be advised to increase the dose of allopurinol incrementally as specified in their treatment plan. No change will be advised in those whose urate levels are already at target. If the patient needs to increase allopurinol there will be an automatic reminder after two weeks prompting the patients to submit updated self-test results which will be handled in the same way as described above. Conversely for participants achieving target levels this will be acknowledged and a request to resubmit readings will be sent on a monthly basis.

Official Title
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Effect of Tight Urate Control in Gouty Arthritis Compared to Usual Care (TICOGA), a Randomised Clinical Trial

Conditions
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Gout

Intervention / Treatment
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* Other: Treat-to-target
* Other: Treat-to-flare


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent. Age ≥18 years. Patient has sustained at least one flare of gout in the previous 12 months. Confirmed clinical diagnosis of gout as per ACR/EULAR criteria Serum urate >0.36mm/L. Patient has a smart phone and is able to install GoutSMART application. Exclusion Criteria: Subject unable to provide consent Patient on maximum urate lowering therapy or where therapy cannot be escalated further due to intolerance/adverse reaction to either allopurinol or febuxostat. End stage renal failure/transplant or established liver disease Current prescription of medication known to interact with xanthine oxidase inhibitors such as azathioprine or mercapto-purine.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treat-to-target<br>All participants will have the GoutSMART application installed on their phones, and be offered a management plan including the use of flare prophylaxis and maximum advised dose of allopurinol based on renal function. All Participants in the treat-to-target group will be provided with a BeneCheck hand-held device and taught to perform urate finger prick self-testing. Participants will be prompted to submit urate readings by the GoutSMART app and if urate levels remain above target their allopurinol will be increased incrementally up to the pre-specified maximum dose of allopurinol. | Other: Treat-to-target<br>* Treatment to achieve urate target using supported self-management approach<br>|
| Active Comparator: Treat-to-flare<br>All participants will have the GoutSMART application installed on their phones, and be offered a management plan including the use of flare prophylaxis and maximum advised dose of allopurinol based on renal function. Participants in the treat-to-flare arm of the study will be reviewed every 4 months and allopurinol dose escalated incrementally if they have sustained a gout flare in the preceding 4 months, up to the maximum pre-specified allopurinol dose. | Other: Treat-to-flare<br>* Treatment escalation based on reported flares of gout<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants flare free in 2nd year of trial | Proportion of participants flare free in 2nd year of trial | 2nd year of trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of flares of gout | Number of flares of gout in year 1, year 2 and over whole course of trial | 2 years | 
| Urate targets of ≤0.3mmol/L or ≤0.36mmol/L | Proportion of participants achieving urate levels of ≤0.3mmol/L or ≤0.36mmol/L at 52 and 104wks | 2 years | 
| Medication compliance | Medication compliance assessed by patient self-report | 2 years | 
| Presence of tophi | Proportion of participants with tophi at week 52 and 104 | 2 years | 
| Quality of life using Eq-5D-5L (Euroqol-5 dimension-5 level instrument) | Self-reported quality of life at week 52 and week 104 using global health score (0 to 100 score with 100 representing best possible health) | 2 years | 
| Societal cost | Number of days lost at work and number of medical appointments or hospital admissions due to gout | 2 years | 
| Time to remission | Time to last flare of gout and time to resolution of tophi | 2 years | 
| User engagement | User engagement with smartphone app (number of reminders needed for each submission) | 2 years | 
| Lifestyle changes | Proportion of patients adopting lifestyle changes | 2 years | 
| Medication prescriptions | Medication compliance assessed by community prescriptions issued | 2 years | 
| Medication metabolite level | Assessed by urinary oxypurinol measure | 2 years |