Maintenance or Withdrawal of Urate Lowering Therapy According to Ultrasound Features in Gout Patients: a Randomised Controlled Trial Stop Treatment In Gout
- Conditions
- Gout Chronic
- Interventions
- Drug: Discontibuation of oral ULTDrug: Maintenance of ULT
- Registration Number
- NCT06956885
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 450
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Discontinuation of urate lowering therapy Discontibuation of oral ULT - Continuation of urate lowering therapy (usual care) Maintenance of ULT -
- Primary Outcome Measures
Name Time Method Proportion of patients experiencing one or more flares At 2 years According to the Gaffo's criteria
- Secondary Outcome Measures
Name Time Method 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 Proportion of patients experiencing one or more flares At 36 months According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)
Mean flare rates At 36 months According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)
US features of gout at MPT1s At 36 months Double contour sign, tophi, aggregates for withdrawal arm
US features of gout at knees At 36 months Double contour sign for withdrawal arm
Urate levels At 36 months Change from baseline of patient's global assessment of disease activity At 36 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
Overall Survival At 36 months Consumption of other drugs At 36 months Colchicine, NSAIDs, steroids using a patient self-reported notebook
Incidence of adverse events and serious adverse events At 36 months According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)
Adherence to ULT At 36 months Assessed by a questionnaire
Change from baseline in Healthrelated quality of life At 36 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 36 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 36 months Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death
estimated glomerular filtration rate (eGFR) At 36 months Renal function
Incidence of comorbidities At 36 months Charlson index Total score varies from 0 to \>=5 The lower the score the higher the estimated 10-year survival