Maintenance or Withdrawal of Urate Lowering Therapy According to Ultrasound Features in Gout Patients: a Randomised Controlled Trial Stop Treatment In Gout (STING)

Maintenance or Withdrawal of Urate Lowering Therapy According to Ultrasound Features in Gout Patients: a Randomised Controlled Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gout Chronic
• Intervention / Treatment: Drug: Discontibuation of oral ULT; Drug: Maintenance of ULT

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Paul Richette, MD PhD; Phone Number: +33 1 49 95 86 31; Email: pierre.moine@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, MD PhD; Phone Number: +33 1 42 49 49 60; Email: jerome.lambert@u-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Discontinuation of urate lowering therapy	Drug: Discontibuation of oral ULT; Patients will stop the ULT at D0. They will have an US scan to look for urate deposits at each visit.
Active Comparator: Continuation of urate lowering therapy (usual care)	Drug: Maintenance 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing one or more flares	According to the Gaffo's criteria	At 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing one or more flares	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 6 months
Proportion of patients experiencing one or more flares	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 12 months
Proportion of patients experiencing one or more flares	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 18 months
Proportion of patients experiencing one or more flares	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 30 months
Proportion of patients experiencing one or more flares	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 36 months
Mean flare rates	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 6 months
Mean flare rates	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 12 months
Mean flare rates	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 18 months
Mean flare rates	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 24 months
Mean flare rates	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 30 months
Mean flare rates	According to both the Gaffo's criteria and the patient-reported Gout Attack Intensity Score (GAIS)	At 36 months
US features of gout at MPT1s	Double contour sign, tophi, aggregates for withdrawal arm	At 6 months
US features of gout at MPT1s	Double contour sign, tophi, aggregates for withdrawal arm	At 12 months
US features of gout at MPT1s	Double contour sign, tophi, aggregates for withdrawal arm	At 18 months
US features of gout at MPT1s	Double contour sign, tophi, aggregates for both arms	At 24 months
US features of gout at MPT1s	Double contour sign, tophi, aggregates for withdrawal arm	At 30 months
US features of gout at MPT1s	Double contour sign, tophi, aggregates for withdrawal arm	At 36 months
US features of gout at knees	Double contour sign for withdrawal arm	At 6 months
US features of gout at knees	Double contour sign for withdrawal arm	At 12 months
US features of gout at knees	Double contour sign for withdrawal arm	At 18 months
US features of gout at knees	Double contour sign for both arms	At 24 months
US features of gout at knees	Double contour sign for withdrawal arm	At 30 months
US features of gout at knees	Double contour sign for withdrawal arm	At 36 months
Urate levels		At 6 months
Urate levels		At 12 months
Urate levels		At 18 months
Urate levels		At 24 months
Urate levels		At 30 months
Urate levels		At 36 months
Change from baseline of patient's global assessment of disease activity	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	At 12 months
Change from baseline of patient's global assessment of disease activity	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	At 24 months
Change from baseline of patient's global assessment of disease activity	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	At 36 months
Change from baseline in Healthrelated quality of life	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	At 12 months
Change from baseline in Healthrelated quality of life	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	At 24 months
Change from baseline in Healthrelated quality of life	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	At 36 months
Change from baseline in Activity limitation	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)	At 12 months
Change from baseline in Activity limitation	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)	At 24 months
Change from baseline in Activity limitation	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)	At 36 months
Incidence of Major CardioVascular events	Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death	At 6 months
Incidence of Major CardioVascular events	Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death	At 12 months
Incidence of Major CardioVascular events	Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death	At 18 months
Incidence of Major CardioVascular events	Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death	At 24 months
Incidence of Major CardioVascular events	Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death	At 30 months
Incidence of Major CardioVascular events	Including nonfatal stroke, nonfatal myocardial infarction, cardiovascular death	At 36 months
estimated glomerular filtration rate (eGFR)	Renal function	At 6 months
estimated glomerular filtration rate (eGFR)	Renal function	At 12 months
estimated glomerular filtration rate (eGFR)	Renal function	At 18 months
estimated glomerular filtration rate (eGFR)	Renal function	At 24 months
estimated glomerular filtration rate (eGFR)	Renal function	At 30 months
estimated glomerular filtration rate (eGFR)	Renal function	At 36 months
Incidence of comorbidities	Charlson index Total score varies from 0 to >=5 The lower the score the higher the estimated 10-year survival	At 12 months
Incidence of comorbidities	Charlson index Total score varies from 0 to >=5 The lower the score the higher the estimated 10-year survival	At 24 months
Incidence of comorbidities	Charlson index Total score varies from 0 to >=5 The lower the score the higher the estimated 10-year survival	At 36 months
Overall Survival		At 12 months
Overall Survival		At 24 months
Overall Survival		At 36 months
Consumption of other drugs	Colchicine, NSAIDs, steroids using a patient self-reported notebook	At 6 months
Consumption of other drugs	Colchicine, NSAIDs, steroids using a patient self-reported notebook	At 12 months
Consumption of other drugs	Colchicine, NSAIDs, steroids using a patient self-reported notebook	At 18 months
Consumption of other drugs	Colchicine, NSAIDs, steroids using a patient self-reported notebook	At 24 months
Consumption of other drugs	Colchicine, NSAIDs, steroids using a patient self-reported notebook	At 30 months
Consumption of other drugs	Colchicine, NSAIDs, steroids using a patient self-reported notebook	At 36 months
Incidence of adverse events and serious adverse events	According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)	At 6 months
Incidence of adverse events and serious adverse events	According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)	At 12 months
Incidence of adverse events and serious adverse events	According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)	At 18 months
Incidence of adverse events and serious adverse events	According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)	At 24 months
Incidence of adverse events and serious adverse events	According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)	At 30 months
Incidence of adverse events and serious adverse events	According to CTCAE v5.0 classification (Common Terminology Criteria for Adverse Events)	At 36 months
Adherence to ULT	Assessed by a questionnaire	At 6 months
Adherence to ULT	Assessed by a questionnaire	At 12 months
Adherence to ULT	Assessed by a questionnaire	At 18 months
Adherence to ULT	Assessed by a questionnaire	At 24 months
Adherence to ULT	Assessed by a questionnaire	At 30 months
Adherence to ULT	Assessed by a questionnaire	At 36 months
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Crystal Arthropathies; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Gout
• Other Study ID Numbers: APHP230854

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No