Clinical trial NCT06956885: Maintenance or Withdrawal of Urate Lowering Therapy According to Ultrasound Features in Gout Patients: a Randomised Controlled Trial Stop Treatment In Gout
Official title: Maintenance or Withdrawal of Urate Lowering Therapy According to Ultrasound Features in Gout Patients: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gout Chronic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-05-04
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 -.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients experiencing one or more flares
timeFrame: At 2 years
Secondary outcomes:
measure: Proportion of patients experiencing one or more flares
timeFrame: At 6 months
measure: Proportion of patients experiencing one or more flares
timeFrame: At 12 months
measure: Proportion of patients experiencing one or more flares
timeFrame: At 18 months
measure: Proportion of patients experiencing one or more flares
timeFrame: At 30 months
measure: Proportion of patients experiencing one or more flares
timeFrame: At 36 months
measure: Mean flare rates
timeFrame: At 6 months
measure: Mean flare rates
timeFrame: At 12 months
measure: Mean flare rates
timeFrame: At 18 months
measure: Mean flare rates
timeFrame: At 24 months
measure: Mean flare rates
timeFrame: At 30 months
measure: Mean flare rates
timeFrame: At 36 months
measure: US features of gout at MPT1s
timeFrame: At 6 months
measure: US features of gout at MPT1s
timeFrame: At 12 months
measure: US features of gout at MPT1s
timeFrame: At 18 months
measure: US features of gout at MPT1s
timeFrame: At 24 months
measure: US features of gout at MPT1s
timeFrame: At 30 months
measure: US features of gout at MPT1s
timeFrame: At 36 months
measure: US features of gout at knees
timeFrame: At 6 months
measure: US features of gout at knees
timeFrame: At 12 months
measure: US features of gout at knees
timeFrame: At 18 months
measure: US features of gout at knees
timeFrame: At 24 months
measure: US features of gout at knees
timeFrame: At 30 months
measure: US features of gout at knees
timeFrame: At 36 months
measure: Urate levels
timeFrame: At 6 months
measure: Urate levels
timeFrame: At 12 months
measure: Urate levels
timeFrame: At 18 months
measure: Urate levels
timeFrame: At 24 months
measure: Urate levels
timeFrame: At 30 months
measure: Urate levels
timeFrame: At 36 months
measure: Change from baseline of patient's global assessment of disease activity
timeFrame: At 12 months
measure: Change from baseline of patient's global assessment of disease activity
timeFrame: At 24 months
measure: Change from baseline of patient's global assessment of disease activity
timeFrame: At 36 months
measure: Change from baseline in Healthrelated quality of life
timeFrame: At 12 months
measure: Change from baseline in Healthrelated quality of life
timeFrame: At 24 months
measure: Change from baseline in Healthrelated quality of life
timeFrame: At 36 months
measure: Change from baseline in Activity limitation
timeFrame: At 12 months
measure: Change from baseline in Activity limitation
timeFrame: At 24 months
measure: Change from baseline in Activity limitation
timeFrame: At 36 months
measure: Incidence of Major CardioVascular events
timeFrame: At 6 months
measure: Incidence of Major CardioVascular events
timeFrame: At 12 months
measure: Incidence of Major CardioVascular events
timeFrame: At 18 months
measure: Incidence of Major CardioVascular events
timeFrame: At 24 months
measure: Incidence of Major CardioVascular events
timeFrame: At 30 months
measure: Incidence of Major CardioVascular events
timeFrame: At 36 months
measure: estimated glomerular filtration rate (eGFR)
timeFrame: At 6 months
measure: estimated glomerular filtration rate (eGFR)
timeFrame: At 12 months
measure: estimated glomerular filtration rate (eGFR)
timeFrame: At 18 months
measure: estimated glomerular filtration rate (eGFR)
timeFrame: At 24 months
measure: estimated glomerular filtration rate (eGFR)
timeFrame: At 30 months
measure: estimated glomerular filtration rate (eGFR)
timeFrame: At 36 months
measure: Incidence of comorbidities
timeFrame: At 12 months
measure: Incidence of comorbidities
timeFrame: At 24 months
measure: Incidence of comorbidities
timeFrame: At 36 months
measure: Overall Survival
timeFrame: At 12 months
measure: Overall Survival
timeFrame: At 24 months
measure: Overall Survival
timeFrame: At 36 months
measure: Consumption of other drugs
timeFrame: At 6 months
measure: Consumption of other drugs
timeFrame: At 12 months
measure: Consumption of other drugs
timeFrame: At 18 months
measure: Consumption of other drugs
timeFrame: At 24 months
measure: Consumption of other drugs
timeFrame: At 30 months
measure: Consumption of other drugs
timeFrame: At 36 months
measure: Incidence of adverse events and serious adverse events
timeFrame: At 6 months
measure: Incidence of adverse events and serious adverse events
timeFrame: At 12 months
measure: Incidence of adverse events and serious adverse events
timeFrame: At 18 months
measure: Incidence of adverse events and serious adverse events
timeFrame: At 24 months
measure: Incidence of adverse events and serious adverse events
timeFrame: At 30 months
measure: Incidence of adverse events and serious adverse events
timeFrame: At 36 months
measure: Adherence to ULT
timeFrame: At 6 months
measure: Adherence to ULT
timeFrame: At 12 months
measure: Adherence to ULT
timeFrame: At 18 months
measure: Adherence to ULT
timeFrame: At 24 months
measure: Adherence to ULT
timeFrame: At 30 months
measure: Adherence to ULT
timeFrame: At 36 months
measure: Incremental Cost effectiveness ratios estimating cost per QALY gained
timeFrame: Up to 36 months
measure: Incremental Cost effectiveness ratios estimating cost per flare avoided.
timeFrame: Up to 36 months
Other outcomes:
Locations:
Study officials:
References: