治療を目的とした血清尿酸塩と痛風の症状を回避するための治療との比較 (TRUST)
痛風における治療対標的血清尿酸塩対治療対回避症状：ランダム化比較試験
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.
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Ana D Fernandes, MA
- 電話番号：617-643-2140
- メール：adfernandes@mgh.harvard.edu
研究場所
-
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Alabama
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South Birmingham、Alabama、アメリカ、35233
- まだ募集していません
- The University of Alabama at Birmingham
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コンタクト：
- Kenneth Saag, MD, MSc
- メール：ksagg@uabmc.edu
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コンタクト：
- Kevin Riggs, MD, MPH
- メール：kriggs@uab.edu
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California
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Santa Monica、California、アメリカ、90404
- まだ募集していません
- UCLA Health
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コンタクト：
- John Fitzgerald, MD, PhD
- メール：Jfitzgerald@mednet.ucla.edu
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コンタクト：
- Paul Shekelle, MD,PhD
- メール：Paul.Shekelle@va.gov
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Massachusetts
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Boston、Massachusetts、アメリカ、02114
- 募集
- Massachusetts General Hospital
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主任研究者：
- Hyon K Choi, MD, DrPH
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コンタクト：
- Ana D Fernandes, MA
- 電話番号：617-643-2140
- メール：adfernandes@mgh.harvard.edu
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Boston、Massachusetts、アメリカ、02115
- 募集
- Brigham and Women's Hospital (BWH)
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コンタクト：
- Daniel H Solomon, MD, MPH
- メール：dsolomon@bwh.harvard.edu
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コンタクト：
- Jacklyn Stratton
- メール：jstratton1@bwh.harvard.edu
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Boston、Massachusetts、アメリカ、02119
- まだ募集していません
- Boston Medical Center (BMC)
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コンタクト：
- Julien J Dedier, MD, MPH
- メール：Julien.Dedier@bmc.org
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New York
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New York、New York、アメリカ、10010
- 募集
- NYU Langone
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コンタクト：
- Michael Pillinger, MD
- メール：Michael.pillinger@nyulangone.org
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コンタクト：
- David Wei, MD
- メール：David.Wei@nyulangone.org
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West Virginia
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Morgantown、West Virginia、アメリカ、26506
- まだ募集していません
- West Virginia University (Including Mobile Clinical Trials Unit)
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コンタクト：
- Sally Hodder, MD
- 電話番号：304-581-1842
- メール：slhodder@hsc.wvu.edu
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コンタクト：
- Maggie Childers-Kakos, MS
- 電話番号：304-293-1426
- メール：margaret.childers@hsc.wvu.edu
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副調査官：
- Sarah Hansen, MD
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副調査官：
- Kimberly Houchin, MD
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副調査官：
- Joanna Bailey, MD
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副調査官：
- Mathew Weimer, MD
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：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.
他の名前：
Naproxen 250 mg p.o. twice daily
他の名前：
Colchicine 0.6 mg p.o. once daily
他の名前：
|
|
アクティブコンパレータ：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.
他の名前：
Naproxen 250 mg p.o. twice daily
他の名前：
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.
他の名前：
dose escalation to 500 mg twice daily for patients experiencing breakthrough flares.
他の名前：
For flare glucocorticoids: prednisone taper for 8 days, starting with 40mg (oral) daily.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Frequency of gout flare
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Quality of life assessment
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Hyon K Choi, MD, PhD、Massachusetts General Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2021P000517
- 1U01AR080985-01A1 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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