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

Gout Clinical Trial

— TRUST  

Official title:

Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout: A Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04875702
• Other study ID #: 2021P000517
• Secondary ID: 1U01AR080985-01A
• Status: Recruiting
• Phase: Phase 4
• Start date: January 23, 2024
• Est. completion date: November 2028

Study information

• Verified date: March 2024
• Source: Massachusetts General Hospital
• Contact: Ana D Fernandes, MA
• Phone: 617-643-2140
• Email: adfernandes[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 650
• Est. completion date: November 2028
• Est. primary completion date: November 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

To be eligible to be enrolled in the study, each patient must:

1. Provide signed written 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) = 7.0 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 a written informed consent

5. ALT > 3 × upper limit of normal (ULN) (within 6 months of entry);

6. Pregnancy, planning pregnancy, or breastfeeding;

7. Taking mercaptopurine (PURINETHOL®) or azathioprine (IMURAN®);

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; or

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.

Candidates who meet any of the following criteria will be excluded from the study:

• Diagnosis of chronic kidney disease (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 a written informed consent;

• alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN) (within 6 months of entry);

• Pregnancy, planning pregnancy, or breastfeeding;

• Taking mercaptopurine (PURINETHOL®) or azathioprine (IMURAN®);

• Unlikely to survive 2 years because of comorbidities; or

• Currently taking > 200 mg per day of allopurinol. 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.

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• 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.
• Naproxen 250 MG
Naproxen 250 mg p.o. twice daily
• Colchicine 0.6 mg
Colchicine 0.6 mg p.o. once daily
• 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.
• Naproxen 500 Mg
dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.
• Prednisone 40 mg
For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.

Locations

Country	Name	City	State
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Medical Center (BMC)	Boston	Massachusetts
United States	Brigham and Women's Hospital (BWH)	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	NYU Langone	New York	New York
United States	UCLA Health	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of gout flare	number of gout flares occurring during two years of follow-up between the TTT-SU and TTASx groups	baseline to two years of follow up
Secondary	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.	baseline to two years of follow up