Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout

Phase 4RecruitingNCT04875702

Massachusetts General Hospital650 enrolled

Overview

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.

This trial aims to answer a fundamental question in the management of gout by comparing two commonly used treatment strategies for gout (TTT vs TTASx) to determine which is most beneficial for a range of patient-centered gout outcomes, as well as relevant CV-metabolic-renal endpoints. Designing a scientifically valid and pragmatic clinical trial involves numerous tradeoffs in study design, subject eligibility criteria, and outcome measurement. We have come together as primary care physicians and rheumatologists to consider several alternative designs. We first considered the target study population. Since most rheumatologists believe that the TTT approach is superior, it would be difficult to recruit from rheumatology practices. Thus, we aimed to design a trial that would be feasible to conduct in primary care practices, with an intervention that could primarily be run by nurses and physician assistants. This design would be pragmatic and generalizable to primary care practices outside of the setting of a randomized controlled trial. The trial also needs to incorporate the perspectives of rheumatologists, primary care clinicians, allied specialists, and patients when deciding the key issues to be addressed and how best to answer these questions.76 We convened a modified Delphi Panel (mDP) to solicit input using a formal process of voting and discussion. The Delphi Panel is a commonly used approach in health care for areas where there is less than perfect data to make decisions. It also has been used in the social sciences as a method for formalizing input from multiple parties, using voting and discussion.77,78 We selected a broadly representative group of mDP panelists from four categories of constituents who could inform the trial design: patients, nurses, primary care physicians, and rheumatologists. Two voting rounds were held, including a video conference meeting to discuss all the voting questions and re-vote on items where no consensus had been reached on the first round.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

650

Conditions

Gout

Interventions

AllopurinolDRUG

For the TTT-SU group: The dose titration algorithm for allopurinol increases every 4 weeks by 100 mg until the target serum urate of 6 mg/dL is reached or a patient requires 800 mg per day of allopurinol. Subjects will require a blood draw for SU every 4 weeks until reaching the target. For the TTASx group: Subjects randomized to the TTASx group will receive anti-inflammatory treatments (naproxen, colchicine, and/or prednisone) for up to six flares over the ensuing three months. Urate lowering therapy (ULT) will only be offered after the third flare during the trial.

Naproxen 250 MGDRUG

Naproxen 250 mg p.o. twice daily

Colchicine 0.6 mgDRUG

Colchicine 0.6 mg p.o. once daily

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

To be eligible to be enrolled in the study, each patient must: 1. Provide signed written or electronic informed consent. 2. Be between 18 and 90 years old. 3. Be in a participating primary care practice with at least one visit in the previous 36 months. 4. Be diagnosed with gout by the 2015 ACR/EULAR criteria, with 8 or more points on the 2015 ACR/EULAR criteria scoring algorithm. 5. Have experienced at least one gout flare attributed in the previous 12 months. 6. Have a baseline inter-critical serum urate (SU) ≥ 6.0 mg/dL (at screening or in the 30 days before screening) 7. Be able to swallow pills. 8. Agree to practice effective measures of birth control if of reproductive potential. Exclusion Criteria Candidates who meet any of the following criteria will be excluded from the study: 1. Diagnosis of CKD Stage 3B or worse (eGFR \< 45 mL/min/ 1.73 m2) at screening 2. More than one subcutaneous tophus on clinical examination at screening 3. Two or more episodes of renal colic in the past 5 years 4. Unable to provide informed consent. 5. AST/ALT \> 3 × upper limit of normal (ULN) (within 6 months of entry). 6. Pregnancy, planning pregnancy, or breastfeeding. 7. Patients who have been treated with thiopurines (mercaptopurine (PURINETHOL®), azathioprine (IMURAN®), or thioguanine) in the past 12 months or currently being treated with thiopurines are not eligible for the study. Usage of the thiopurines (azathioprine and mercaptopurine) with allopurinol has been shown to cause a significant drug-drug interaction. 8. Unlikely to survive 2 years because of comorbidities. 9. Currently taking \> 200 mg of allopurinol per day or any dose of febuxostat. Patients taking 200 mg or less of allopurinol daily may participate, provided they meet the eligibility criteria for flares and current SU, and they have not had a dose escalation in their allopurinol in the previous 6 months. 10. Patients with known allergic or hypersensitive reactions to allopurinol and not willing to initiate febuxostat if urate lowering is indicated. 11. Subjects that test positive for HLA-B\*5801 allele, a genetic marker for severe cutaneous adverse reactions caused by allopurinol and are unwilling to initiate febuxostat if urate lowering is indicated by the study. Subjects of higher risk, including Black/African American, Asian (except Japanese), native Hawaiian, or Pacific Islander descent will be tested at screening.

Locations (7)

The University of Alabama at Birmingham

South Birmingham, Alabama, United States

NOT_YET_RECRUITING

UCLA Health

Santa Monica, California, United States

NOT_YET_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Frequency of gout flare

number of gout flares occurring during two years of follow-up between the TTT-SU and TTASx groups

Time frame: baseline to two years of follow up

Secondary Outcomes

Quality of life assessment

The Short Form 36 Health Survey Questionnaire (SF-36) questionnaire will be used to assess the health status of study participants by surveying 36 questions in 8 domains of health. A higher score indicates a better health status. For the TRUST study a total physical (score of 10 to 30), functional (a score of 4 to 8) and pain (a score of 2 to 11) will be used as the secondary outcome.

Time frame: baseline to two years of follow up

Central Contacts

Ana D Fernandes, MA

CONTACT

617-643-2140 adfernandes@mgh.harvard.edu

Data from ClinicalTrials.gov

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