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

NCT ID: NCT04875702

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 650 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-22
• Study Completion Date: 2028-10-31

Brief Summary

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.

Detailed Description

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.

Conditions

Gout

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TTT-SU

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.

Group Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

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 MG

Intervention Type: DRUG

Naproxen 250 mg p.o. twice daily

Colchicine 0.6 mg

Intervention Type: DRUG

Colchicine 0.6 mg p.o. once daily

TTASx

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 Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

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 MG

Intervention Type: DRUG

Naproxen 250 mg p.o. twice daily

Colchicine 1.2 mg

Intervention Type: DRUG

Dose escalation to 0.6 mg p.o. twice daily for patients experiencing breakthrough flares or a dose decrease (0.6 mg p.o. every other day) for patients experiencing gastrointestinal intolerance.

Naproxen 500 Mg

Intervention Type: DRUG

dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.

Prednisone 40 mg

Intervention Type: DRUG

For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.

Interventions

Allopurinol

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.

Intervention Type: DRUG

Naproxen 250 MG

Naproxen 250 mg p.o. twice daily

Intervention Type: DRUG

Colchicine 0.6 mg

Colchicine 0.6 mg p.o. once daily

Intervention Type: DRUG

Colchicine 1.2 mg

Dose escalation to 0.6 mg p.o. twice daily for patients experiencing breakthrough flares or a dose decrease (0.6 mg p.o. every other day) for patients experiencing gastrointestinal intolerance.

Intervention Type: DRUG

Naproxen 500 Mg

dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.

Intervention Type: DRUG

Prednisone 40 mg

For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.

Intervention Type: DRUG

Other Intervention Names

Aloprim, Zyloprim; Prophylaxis; Prophylaxis; Flare; Flare; Flare

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hyon Choi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hyon K Choi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

The University of Alabama at Birmingham

South Birmingham, Alabama, United States

Site Status: NOT_YET_RECRUITING

UCLA Health

Santa Monica, California, United States

Site Status: NOT_YET_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Brigham and Women's Hospital (BWH)

Boston, Massachusetts, United States

Site Status: RECRUITING

Boston Medical Center (BMC)

Boston, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

NYU Langone

New York, New York, United States

Site Status: RECRUITING

West Virginia University (Including Mobile Clinical Trials Unit)

Morgantown, West Virginia, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Ana D Fernandes, MA

Role: CONTACT

adfernandes@mgh.harvard.edu

617-643-2140

Facility Contacts

Kenneth Saag, MD, MSc

Role: primary

ksagg@uabmc.edu

Kevin Riggs, MD, MPH

Role: backup

kriggs@uab.edu

John Fitzgerald, MD, PhD

Role: primary

Jfitzgerald@mednet.ucla.edu

Paul Shekelle, MD,PhD

Role: backup

Paul.Shekelle@va.gov

Ana D Fernandes, MA

Role: primary

adfernandes@mgh.harvard.edu

617-643-2140

Daniel H Solomon, MD, MPH

Role: primary

dsolomon@bwh.harvard.edu

Jacklyn Stratton

Role: backup

jstratton1@bwh.harvard.edu

Julien J Dedier, MD, MPH

Role: primary

Julien.Dedier@bmc.org

Michael Pillinger, MD

Role: primary

Michael.pillinger@nyulangone.org

David Wei, MD

Role: backup

David.Wei@nyulangone.org

Sally Hodder, MD

Role: primary

slhodder@hsc.wvu.edu

304-581-1842

Maggie Childers-Kakos, MS

Role: backup

margaret.childers@hsc.wvu.edu

304-293-1426

Other Identifiers

1U01AR080985-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2021P000517

Identifier Type: -

Identifier Source: org_study_id