Gout Chronic
Conditions
Brief summary
According to international recommendations, urate lowering therapy (ULT), mainly the xanthine oxidase inhibitors (XOIs) allopurinol and febuxostat, should be prescribed lifelong in gout patients. However, this recommendation comes up against very poor adherence to ULT, since around half of patients stop their treatment at 5 years. Moreover, there is uncertainty about the cardiovascular tolerance of febuxostat taken over the long term. Finally, although XOIs are generally well tolerated, they can cause side effects and require regular biological monitoring. The hypothesis is that the risk of flares following withdrawal of ULT is very low in gout patients when urate store is depleted and repeated ultrasounds (US) do not demonstrate the reappearance of urate deposits.
Interventions
DRUGDiscontibuation of oral ULT
Patients will stop the ULT at D0. They will have an US scan to look for urate deposits at each visit.
DRUGMaintenance of ULT
Patients will continue their ULT according to the recommendations of the Eular and French Society of Rheumatology, to maintain their SUA levels below 60 mg/l.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicentre, parallel arm, non-blinded randomised controlled non-inferiority clinical trial. Gout patients in remission and no urate deposits as assessed by US will be randomised to i) a maintenance group -ULT will be pursued - or ii) a withdrawal experimental group - discontinuation of ULT -.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Gout, defined according to the 2015 ACR/EULAR classification criteria * No flares for at least 2 years * No tophi * Currently receiving allopurinol or febuxostat taken for at least 2 years and SUA levels ≤ 60 mg/l * No urate deposit on ultrasound at inclusion visit at both MTPs 1 and knees * Ability to provide informed consent * Women of childbearing potential (WOCBP) are required to have a negative pregnancy test before treatment and must agree to maintain during treatment highly effective contraception (ie,abstinence, combined estrogen- and progestogen-containing hormonal contraception, ovulation inhibitors (Oral, Intravaginal, Transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (Oral, Injectable, Implantable); Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised partner). * Health Insurance
Exclusion criteria
* Unstable systemic medical condition (e.g., New York Heart Association stage IV heart failure, recent myocardial infarction, advanced cancer) * History of allergy to allopurinol or febuxostat or one of the excipients * Association with azathioprine, mercaptopurine (cytostatics-antimetabolites) * Contraindications to experimental medicinal products or auxiliary medicinal products * CKD stage 4 (eGFR less than 30 ml/mn/1.73 m2) * Ongoing treatment with uricosurics (benzbromarone and probenecid) or uricase * Patient on SMA (state medical aid-AME) * Participation in other clinical trial on medicinal product for human use * Lack of contraception for women of childbearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients experiencing one or more flares | At 2 years | According to the Gaffo's criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients experiencing one or more flares | At 6 months | According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS) |
| Mean flare rates | At 6 months | According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS) |
| US features of gout at MPT1s | At 6 months | Double contour sign, tophi, aggregates for withdrawal arm |
| US features of gout at knees | At 6 months | Double contour sign for withdrawal arm |
| Change from baseline of patient's global assessment of disease activity | At 12 months | Outcome Measures in Rheumatology (OMERACT) core outcome domains for long-term gout studies 0-5-point Likert scale, the higher the score the more severe the disease |
| Change from baseline in Healthrelated quality of life | At 12 months | Outcome Measures in Rheumatology (OMERACT) core outcome domains for long-term gout studies EuroQol 5-domain-3L (EQ-5D3L) questionnaire The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems |
| Change from baseline in Activity limitation | At 12 months | Outcome Measures in Rheumatology (OMERACT) core outcome domains for long-term gout studies Health Assessment Questionnaire II is a 10-item score. Each item is rated on a 4-point Likert scale HAQ-II mean score ranges from 0 (no disability) to 3 (severe disability) |
| Incidence of Major CardioVascular events | At 6 months | Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death |
| Urate levels | At 6 months | — |
| Incidence of comorbidities | At 12 months | Charlson index Total score varies from 0 to \>=5 The lower the score the higher the estimated 10-year survival |
| Overall Survival | At 12 months | — |
| Consumption of other drugs | At 6 months | Colchicine, NSAIDs, steroids using a patient self-reported notebook |
| Incidence of adverse events and serious adverse events | At 6 months | According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events) |
| Adherence to ULT | At 6 months | Assessed by a questionnaire |
| Incremental Cost effectiveness ratios estimating cost per QALY gained | Up to 36 months | — |
| Incremental Cost effectiveness ratios estimating cost per flare avoided. | Up to 36 months | — |
| estimated glomerular filtration rate (eGFR) | At 6 months | Renal function |
Contacts
Primary ContactPaul Richette, MD PhD
Backup ContactJérôme Lambert, MD PhD
Outcome results
None listed