GoutPhase 4TRUSTNCT04875702
Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout
A Phase 4 study testing Allopurinol, Naproxen 250 MG and Colchicine 0.6 mg in people with Gout, run by Massachusetts General Hospital at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Gout
- What is being tested?
- Allopurinol, Naproxen 250 MG and Colchicine 0.6 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 650 participants
- Where
- 7 sitesUnited States
- Study dates
- 22 Feb 2024to 31 Oct 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Candidates who meet any of the following criteria will be excluded from the study:
- Diagnosis of CKD Stage 3B or worse (eGFR < 45 mL/min/ 1.73 m2) at screening
- More than one subcutaneous tophus on clinical examination at screening
- Two or more episodes of renal colic in the past 5 years
- Unable to provide informed consent.
- AST/ALT > 3 × upper limit of normal (ULN) (within 6 months of entry).
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- Pregnancy, planning pregnancy, or breastfeeding.
- 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.
- Unlikely to survive 2 years because of comorbidities.
- 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.
- Patients with known allergic or hypersensitive reactions to allopurinol and not willing to initiate febuxostat if urate lowering is indicated.
- 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ana D Fernandes, MA, 617-643-2140, adfernandes@mgh.harvard.edu
Hyon K Choi, MD, DrPH
- Recruiting
Brigham and Women's Hospital (BWH)
Boston, Massachusetts, 02115
Daniel H Solomon, MD, MPH, dsolomon@bwh.harvard.edu
Jacklyn Stratton, jstratton1@bwh.harvard.edu
- Not yet recruiting
Boston Medical Center (BMC)
Boston, Massachusetts, 02119
Julien J Dedier, MD, MPH, Julien.Dedier@bmc.org
- Not yet recruiting
West Virginia University (Including Mobile Clinical Trials Unit)
Morgantown, West Virginia, 26506
Sally Hodder, MD, 304-581-1842, slhodder@hsc.wvu.edu
Maggie Childers-Kakos, MS, 304-293-1426, margaret.childers@hsc.wvu.edu
- Recruiting
NYU Langone
New York, New York, 10010
Michael Pillinger, MD, Michael.pillinger@nyulangone.org
David Wei, MD, David.Wei@nyulangone.org
- Not yet recruiting
UCLA Health
Santa Monica, California, 90404
John Fitzgerald, MD, PhD, Jfitzgerald@mednet.ucla.edu
Paul Shekelle, MD,PhD, Paul.Shekelle@va.gov
- Not yet recruiting
The University of Alabama at Birmingham
South Birmingham, Alabama, 35233
Kenneth Saag, MD, MSc, ksagg@uabmc.edu
Kevin Riggs, MD, MPH, kriggs@uab.edu
About this study
Official title: Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout: A Randomized Controlled 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.
Read the 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
- Being tested
- Allopurinol, Naproxen 250 MG, Colchicine 0.6 mg, Colchicine 1.2 mg, Naproxen 500 Mg
- Medical subject headings
- Gout
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
Also called Aloprim, Zyloprim
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
Also called Prophylaxis
Naproxen 250 mg p.o. twice daily
Colchicine 0.6 mgDrug
Also called Prophylaxis
Colchicine 0.6 mg p.o. once daily
Colchicine 1.2 mgDrug
Also called Flare
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 MgDrug
Also called Flare
dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.
Prednisone 40 mgDrug
Also called Flare
For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.
| Study group | Role | What they receive |
|---|---|---|
| TTT-SU | Active comparator | 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. Receives: Drug: Allopurinol; Drug: Naproxen 250 MG; Drug: Colchicine 0.6 mg |
| TTASx | Active comparator | 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. Receives: Drug: Allopurinol; Drug: Naproxen 250 MG; Drug: Colchicine 1.2 mg; Drug: Naproxen 500 Mg; Drug: Prednisone 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of gout flare
number of gout flares occurring during two years of follow-up between the TTT-SU and TTASx groups
Measured: baseline to two years of follow up
Secondary outcomes (1)
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.
Measured: baseline to two years of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start22 Feb 2024
- Primary completion1 Sep 2028 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GoutStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 650 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Hyon Choi, Massachusetts General Hospital
- Investigators
- Hyon K Choi, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04875702
- Sponsor's protocol ID
- 2021P000517
- Other IDs
- 1U01AR080985-01A1
- Acronym
- TRUST
- Status last verified
- Sep 2025
- First submitted
- 3 May 2021
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No