Treat-to-Target vs Symptom Management for Gout
(TRUST Trial)
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Thiopurines, Febuxostat
Disqualifiers: CKD Stage 3B, Pregnancy, others
No Placebo Group
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?The TRUST study is a randomized, controlled multicenter study to evaluate the management of gout by comparing two commonly used treatment strategies for gout (TTT vs TTASx) to determine the most beneficial for a patient-centered gout outcomes, as well as relevant cardiovascular-metabolic-renal endpoints.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but if you are taking more than 200 mg of allopurinol per day or any dose of febuxostat, you cannot participate. If you are taking 200 mg or less of allopurinol daily, you may participate if you meet other criteria.
What data supports the effectiveness of the drug Allopurinol for treating gout?
Allopurinol is effective in lowering uric acid levels, which helps prevent gout flares and manage chronic gout. However, adherence to the medication is crucial for optimal outcomes, and switching from brand to generic formulations may affect its effectiveness.
12345Is allopurinol safe for humans?
Allopurinol is generally used to treat gout, but it can cause rare and serious allergic reactions, including skin rashes and severe conditions like Stevens-Johnson syndrome. These reactions can be life-threatening, so it's important to monitor for any unusual symptoms when taking this medication.
23567How is the drug Allopurinol unique in treating gout?
Allopurinol is unique in treating gout because it uses a 'treat-to-target' strategy, which involves setting specific treatment goals and regularly adjusting the medication to achieve those goals, similar to its use in managing other chronic conditions like rheumatoid arthritis.
89101112Eligibility Criteria
This trial is for adults aged 18-90 with chronic kidney disease stage 3B or worse, at least one gout flare in the past year, and high serum urate levels. They must have had two episodes of renal colic within five years and more than one tophus. Participants need to be able to swallow pills and agree to birth control measures if applicable.Inclusion Criteria
Have a baseline inter-critical serum urate (SU) ≥ 7.0 mg/dL (at screening or in the 30 days before screening)
I am between 18 and 90 years old.
Be diagnosed with gout by the 2015 ACR/EULAR criteria, with 8 or more points on the 2015 ACR/EULAR criteria scoring algorithm
+5 more
Exclusion Criteria
Unlikely to survive 2 years because of comorbidities
My kidney function is low, with an eGFR below 45.
I have more than one visible bump under my skin.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either the TTT-SU or TTASx treatment strategy for gout management over three months
3 months
Follow-up
Participants are monitored for safety and effectiveness after treatment, with a focus on gout flare frequency and quality of life
2 years
Participant Groups
The TRUST study compares two gout treatment strategies: Treat-to-Target Serum Urate (TTT) versus Treat-to-Avoid Symptoms (TTASx). It aims to find out which approach is better for patient-centered outcomes and cardiovascular-metabolic-renal health.
2Treatment groups
Active Control
Group I: TTASxActive Control5 Interventions
Subjects randomized to the treat-to-avoid-symptoms (TTASx) group will receive the same education as the TTT-SU group. In addition, they will receive anti-inflammatory treatments (naproxen, colchicine, and/or prednisone); enough to treat up to six flares over the ensuing three months.
Group II: TTT-SUActive Control3 Interventions
The participants randomized to the Treat-to-Target-Serum Urate (TTT-SU) group will be counseled about gout, generalized lifestyle and dietary issues and will be provided with a three-month supply of allopurinol as well as a treatment to prophylax against attacks that might occur during the up-titration of urate lowering therapy. Allopurinol dose increases will occur until SU concentrations achieve a target level \< 6.0 mg/dL.
Allopurinol is already approved in United States, European Union, Canada, Japan, Australia for the following indications:
🇺🇸 Approved in United States as Zyloprim for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
🇪🇺 Approved in European Union as Zyloric for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
🇨🇦 Approved in Canada as Allopurinol for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
🇯🇵 Approved in Japan as Allopurinol for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
🇦🇺 Approved in Australia as Allopurinol for:
- Gout
- Kidney stones
- High uric acid levels after chemotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's Hospital (BWH)Boston, MA
Massachusetts General HospitalBoston, MA
The University of Alabama at BirminghamBirmingham, AL
UCLA HealthSanta Monica, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Collaborator
References
Allopurinol Medication Adherence as a Mediator of Optimal Outcomes in Gout Management. [2018]Patient and provider factors, including allopurinol medication adherence, affect gout treatment outcomes.
Management of acute and chronic gouty arthritis: present state-of-the-art. [2018]There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis. During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin. Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy. The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.
Lack of efficacy during the switch from brand to generic allopurinol. [2013]We report for the first time the lack of therapeutic effects after the switch from a brand formulation of allopurinol to a generic one. A 56-year-old man, with a 5 years history of well-treated gout arthropathy with allopurinol (Zyloric(®) 300 mg/die), developed acute gout arthropathy after the switch from the brand formulation of allopurinol to a generic one. Clinical evaluation and laboratory findings confirmed the diagnosis of acute gout arthropathy. Generic formulation of the drug was dismissed and Zyloric(®) was administered with an improvement of both clinical symptoms and laboratory findings. In conclusion, even if generic formulations are considered to have the same effects in comparison to the brand one, more data are necessaries in order to well define their effectiveness and rationale use.
Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims. [2013]Poor compliance with gout medications has been recognized, but seldom studied. We investigated compliance with allopurinol among managed care enrollees suspected to have gout.
Mortality in Patients With Gout Treated With Allopurinol: A Systematic Review and Meta-Analysis. [2022]Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review and meta-analysis aimed to ascertain the association between mortality and the use of allopurinol in patients with gout.
Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. [2022]Allopurinol is the primary therapy for the management of chronic gout. Utilization of allopurinol has increased in tandem with the growing prevalence of gout globally. This exposes more patients to the risk of allopurinol hypersensitivity (AH), a rare adverse reaction characterised by a spectrum of cutaneous reactions and systemic manifestations. Severe forms of AH have been associated with high mortality. The pathophysiology underlying this reaction remains unknown, but several risk factors have been proposed.
Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan. [2016]Allopurinol, a first-line drug used for treating gout, is increasingly prescribed worldwide to patients with asymptomatic hyperuricemia and comorbid renal or cardiovascular diseases. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The overall risks of allopurinol use remain unclear.
Implementation of disease activity measurement for rheumatoid arthritis patients in an academic rheumatology clinic. [2022]Treat-to-target is the recommended strategy for the management of rheumatoid arthritis (RA) and involves regular assessment of disease activity using validated measures and subsequent adjustment of medical therapy if patients are not in remission or low disease activity. Recommendations published in 2012 detailed the preferred disease activity measures but there have been few publications on implementation of disease activity measures in a real-world clinic setting.
Treat to Target in Axial Spondyloarthritis: What Are the Issues? [2022]Treat to Target (T2T) strategy has been widely used in the management of chronic medical conditions, such as hypertension, diabetes, and hypothyroidism, as well as rheumatic diseases, such as rheumatoid arthritis and gout. The purpose of this review is to discuss the importance, feasibility, and challenges in adopting the T2T strategy for the management of axial spondyloarthritis (axSpA).
The need to define treatment goals for systemic lupus erythematosus. [2022]In the current therapeutic climate, mortality rates from systemic lupus erythematosus (SLE) remain unacceptably high. Although new therapies are on the horizon, pending their emergence and availability, optimization of the currently available therapies is potentially achievable. A 'treat-to-target' approach is now considered routine for many diseases, including rheumatoid arthritis, for which it has substantially improved patient outcomes. The heterogeneity of SLE, as well as lack of universal agreement over methods to measure disease activity and treatment responses, has impeded the development of such an approach for this disease. In this article, the potential benefits of a treatment-target definition are explored, obstacles to the development of a treatment target in SLE are identified, and possible strategies to achieve this goal are discussed.
Treatment to target in rheumatoid arthritis. [2016]Treating to target in rheumatoid arthritis means setting defined treatment goals, regularly measuring disease activity and working with, and informing, the patient of these targets at each step. This article discusses the role of the specialist nurse in developing and delivering treatment to target in RA, its impact on patient care and the development of a nurse-led clinic.
Rheumatoid arthritis: recommendations for treat to target. [2014]Integrating the rheumatoid arthritis (RA) treat-to-target concept into standard clinical practice represents a challenge to health professionals. So far, this practice-changing approach has not been widely implemented, in spite of linking its outcome to payment, which was adopted in the best practice tariffs. The recently published revisions in classification criteria and updated recommendations for optimising the use of disease-modifying anti-rheumatic and biologic agents in the treatment of RA paved the way for re-evaluating the standard clinical care models in order to improve patient outcomes, prevent joint damage, and maintain patients' functional ability as well as their quality of life. This article discusses the recent advances in the management of RA and provides a set of recommendations to provide comprehensive guidance for treatment to target with the aim of improving the quality of care for RA patients.