治疗至目标血清尿酸盐与治疗至避免痛风症状 (TRUST)
治疗至目标血清尿酸盐与治疗至避免痛风症状：一项随机对照试验
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.
研究概览
地位
条件
详细说明
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.
研究类型
注册 (估计的)
阶段
- 第四阶段
联系人和位置
学习联系方式
- 姓名：Ana D Fernandes, MA
- 电话号码：617-643-2140
- 邮箱：adfernandes@mgh.harvard.edu
学习地点
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Alabama
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South Birmingham、Alabama、美国、35233
- 尚未招聘
- The University of Alabama at Birmingham
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接触：
- Kenneth Saag, MD, MSc
- 邮箱：ksagg@uabmc.edu
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接触：
- Kevin Riggs, MD, MPH
- 邮箱：kriggs@uab.edu
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California
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Santa Monica、California、美国、90404
- 尚未招聘
- UCLA Health
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接触：
- John Fitzgerald, MD, PhD
- 邮箱：Jfitzgerald@mednet.ucla.edu
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接触：
- Paul Shekelle, MD,PhD
- 邮箱：Paul.Shekelle@va.gov
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Massachusetts
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Boston、Massachusetts、美国、02114
- 招聘中
- Massachusetts General Hospital
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首席研究员：
- Hyon K Choi, MD, DrPH
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接触：
- Ana D Fernandes, MA
- 电话号码：617-643-2140
- 邮箱：adfernandes@mgh.harvard.edu
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Boston、Massachusetts、美国、02115
- 招聘中
- Brigham and Women's Hospital (BWH)
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接触：
- Daniel H Solomon, MD, MPH
- 邮箱：dsolomon@bwh.harvard.edu
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接触：
- Jacklyn Stratton
- 邮箱：jstratton1@bwh.harvard.edu
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Boston、Massachusetts、美国、02119
- 尚未招聘
- Boston Medical Center (BMC)
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接触：
- Julien J Dedier, MD, MPH
- 邮箱：Julien.Dedier@bmc.org
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New York
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New York、New York、美国、10010
- 招聘中
- NYU Langone
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接触：
- Michael Pillinger, MD
- 邮箱：Michael.pillinger@nyulangone.org
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接触：
- David Wei, MD
- 邮箱：David.Wei@nyulangone.org
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West Virginia
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Morgantown、West Virginia、美国、26506
- 尚未招聘
- West Virginia University (Including Mobile Clinical Trials Unit)
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接触：
- Sally Hodder, MD
- 电话号码：304-581-1842
- 邮箱：slhodder@hsc.wvu.edu
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接触：
- Maggie Childers-Kakos, MS
- 电话号码：304-293-1426
- 邮箱：margaret.childers@hsc.wvu.edu
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副研究员：
- Sarah Hansen, MD
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副研究员：
- Kimberly Houchin, MD
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副研究员：
- Joanna Bailey, MD
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副研究员：
- Mathew Weimer, MD
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
To be eligible to be enrolled in the study, each patient must:
- Provide signed written or electronic 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) ≥ 6.0 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 informed consent.
- AST/ALT > 3 × upper limit of normal (ULN) (within 6 months of entry).
- 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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：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. |
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.
其他名称：
Naproxen 250 mg p.o. twice daily
其他名称：
Colchicine 0.6 mg p.o. once daily
其他名称：
|
|
有源比较器：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. |
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.
其他名称：
Naproxen 250 mg p.o. twice daily
其他名称：
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.
其他名称：
dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.
其他名称：
For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Frequency of gout flare
大体时间：baseline to two years of follow up
|
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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Quality of life assessment
大体时间：baseline to two years of follow up
|
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
|
合作者和调查者
调查人员
- 首席研究员：Hyon K Choi, MD, PhD、Massachusetts General Hospital
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 2021P000517
- 1U01AR080985-01A1 (美国 NIH 拨款/合同)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
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