Mass General - Division of Clinical Research

Condition

Gout

Eligibility

Eligible Ages: Between 18 Years and 90 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Criteria

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.

Study Design

Phase: Phase 4
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Double (Participant, Outcomes Assessor)

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator 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.	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. Other names: Aloprim, Zyloprim Drug: Naproxen 250 MG Naproxen 250 mg p.o. twice daily Other names: Prophylaxis Drug: Colchicine 0.6 mg Colchicine 0.6 mg p.o. once daily Other names: Prophylaxis
Active Comparator 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.	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. Other names: Aloprim, Zyloprim Drug: Naproxen 250 MG Naproxen 250 mg p.o. twice daily Other names: Prophylaxis 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. Other names: Flare Drug: Naproxen 500 Mg dose escalation to 500 mg twice daily for patients experiencing breakthrough flares. Other names: Flare Drug: Prednisone 40 mg For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily. Other names: Flare

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

Contact:
Ana D Fernandes, MA
617-643-2140
adfernandes@mgh.harvard.edu

More Details

Status: Recruiting
Sponsor: Massachusetts General Hospital

Study Contact

Ana D Fernandes, MA
617-643-2140
adfernandes@mgh.harvard.edu

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.