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.
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.
Eligibility
To be eligible to be enrolled in the study, each patient must:
- Provide signed written informed consent
- Be between 18 and 90 years old
- Be in a participating primary care practice with at least one visit in the previous 36 months
- Be diagnosed with gout by the 2015 ACR/EULAR criteria, with 8 or more points on the 2015 ACR/EULAR criteria scoring algorithm
- Have experienced at least one gout flare attributed in the previous 12 months
- Have a baseline inter-critical serum urate (SU) ≥ 7.0 mg/dL (at screening or in the 30 days before screening)
- Be able to swallow pills
- 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:
- 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 a written informed consent
- 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;
- 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; or
- 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.