T2Tアプローチによる関節リウマチ患者の治療決定を導く超音波 (US-RA-T2T)
Population
Patients with a diagnosis of Rheumatoid Arthritis (RA), moderate or high clinical disease activity (CDAI>10) despite conventional synthetic (cs)DMARD(s) or bs-ts-DMARDs therapy for ≥3 months, and a maximum of 2 swollen joints (out of 44 joints)
Study design
Randomised multicentre, parallel-arm clinical study
Primary objective
Non-inferiority of the experimental arm (i.e. clinical therapy together with ultrasound guided treatment decision) in comparison to the control arm (clinically guided decision) concerning the proportion of patients reaching low disease activity (CDAI ≤10) and a minimal clinical important improvement (MCII: improvement of ≥6 points if starting from moderate disease activity, any case starting from high disease activity and achieving low disease activity) or remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission) at week 24.
Intervention
This is a randomised multicentre, national, parallel-arm clinical study. Patients with a diagnosis of RA, moderate or high clinical disease activity (CDAI>10) despite conventional synthetic (cs)DMARD(s) or b-tsDMARDs therapy for ≥3 months, and a maximum of 2 swollen joints (out of 44 joints) will be included and randomized to one of the following two strategic arms:
- Clinical decision strategy: All patients receive a new course of b-ts-DMARDs, with or without concomitant cDMARD. If a CDAI ≤10 is not achieved after 12 weeks, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use at week 12 is at the discretion of the investigator.
- Clinical plus ultrasound-based decision strategy. All patients in this group will be evaluated by ultrasound at 44 joints. In case of clinically-verified plus ultrasound verified inflammation, patients will receive a new b-ts-DMARD while continuing or not background csDMARD(s) therapy. If a CDAI ≤10 is not achieved after 12 weeks, patients are again evaluated by ultrasound at 44 joints. In case clinically-verified plus ultrasound-verified inflammation is present, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use is at the discretion of the investigator. In case clinically-verified plus ultrasound-verified inflammation is absent, patients receive step-up pain therapy while background treatment will be continued.
Sample size
158 patients
Time plan
- Total duration of the study: 72 months
- Active phase for each patient: 48 weeks (24 weeks for the interventional treatment strategy and 24 weeks for follow-up visit)
- Recruitment: 60 months
調査の概要
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Christian Dejaco, MD, PhD
- 電話番号：+390474581862
- メール：Christian.Dejaco@sabes.it
研究場所
-
-
Bolzano
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Bruneck、Bolzano、イタリア、39031
- 募集
- Azienda Sanitaria dell'Alto Adige
-
コンタクト：
- Christian Dejaco, MD, PhD
- 電話番号：+390474581862
- メール：Christian.Dejaco@sabes.it
-
-
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
Inclusion Criteria:
- Classification of RA according to the ACR-EULAR 2010 criteria
- Age of the patients: 18 to 84 years
- Patients with moderate or high disease activity according to CDAI (>10)
- Maximum of 2 clinically swollen joints out of a 44-joint count
- Current stable treatment with a single csDMARD or bDMARD or tsDMARD for at least 3 months
- No glucocorticoid therapy or stable glucocorticoid dose for at least 4 weeks and at a maximum dose of 5 mg/day prednisone equivalent.
- No corticosteroid intraarticular injection within 4 weeks
- Stable or absent dose of NSAIDs for at least 1 week
- Patients able and willing to give written informed consent and compliant with the requirements of the study protocol
Exclusion Criteria:
- Complete (clinically evident) destruction of any joint to be investigated by ultrasound as judged by the physician
- Current RA-related vasculitis or other active systemic (i.e. extraarticular) RA-manifestation except for rheumatoid nodules, which in the opinion of the investigator would expose the study subject to a high risk of morbidity or mortality
- Initial arthritis manifestations before the age of 18 years
- Planned surgery within the study period for any of the joints investigated either clinically or by sonography
- Current severe medical illness requiring hospitalization
- Active infection or active malignancy at screening <5 years
- Any contraindication to b/ts DMARDs according to the "Summary of Product Characteristics"
- Pregnancy or lactation
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：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
介入なし：Conventional decision strategy
All patients receive a new course of b-ts-DMARDs, with or without concomitant cDMARD. If a CDAI ≤10 is not achieved after 12 weeks, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use at week 12 is at the discretion of the investigator. |
|
|
実験的：Clinical plus ultrasound-based decision strategy
All patients in this group will be evaluated by ultrasound at 44 joints. In case of clinically-verified plus ultrasound verified inflammation, patients will receive a new b-ts-DMARD while continuing or not background csDMARD(s) therapy. If a CDAI ≤10 is not achieved after 12 weeks, patients are again evaluated by ultrasound at 44 joints. In case clinically-verified plus ultrasound-verified inflammation is present, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use is at the discretion of the investigator. In case clinically-verified plus ultrasound-verified inflammation is absent, patients receive step-up pain therapy while background treatment will be continued. |
At baseline and at weeks 12, 24 and 48, patients will undergo an ultrasound examination of 44 joints by one investigator, who is blinded to the strategic arm and all clinical data. The following joints will be assessed: bilateral wrists (distal radio-ulnar joint, radio-carpal, mid-carpal recesses), 1st - 5th MCP, 1st - 5th PIP, elbows, glenohumeral, acromioclavicular, sternoclavicular, knees, ankles and 1st - 5th MTP. At wrists, MCP and PIP joints, palmar and dorsal sites including synovial recess, extensor and flexor tendons will be investigated whereas at feet the dorsal site (plus the lateral aspects of MTP5) including synovial recess and extensor tendons will be evaluated. Further, we will assess the following: at elbows the dorsal and anterior recess, at shoulders the dorsal recess, at knees the suprapatellar as well as the medial and lateral femoro-tibial recess and at ankles the anterior, lateral and medial recess of the tibiotalar joint. |
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 |
|---|---|---|
|
Non-inferiority of ultrasound-based decision strategy compared to clinically-based strategy.
時間枠：24 weeks
|
Non-inferiority of the experimental arm (i.e. clinical plus ultrasound-guided treatment decision) in comparison to the control arm (clinically-guided decision) concerning the proportion of patients reaching low disease activity (CDAI ≤10) and a minimal clinical important improvement (MCII: improvement of ≥6 points if starting from moderate disease activity, any case achieving low disease activity who started from high disease activity) [19] or remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission) at week 24. |
24 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
12週および48週でのACR/EULAR指数ベースの寛解基準に従った、低疾患活動性およびMCIIまたは寛解の患者の割合の比較
時間枠：12週と48週
|
12週と48週
|
|
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12、24、および48週でのACR / EULARインデックスベースの寛解基準（それぞれCDAI ≤2.8 /ブール寛解）による寛解中の患者の割合の比較
時間枠：12週、24週、48週
|
12週、24週、48週
|
|
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12、24、および48週でのDAS-28（DAS-28 ≤2.6）またはSDAI（≤3.3）による寛解中の患者の割合の比較
時間枠：12週、24週、48週
|
12週、24週、48週
|
|
|
12週目、24週目、48週目の圧痛関節数の比較
時間枠：12週、24週、48週
|
12週、24週、48週
|
|
|
12週、24週、48週の関節腫脹数の比較
時間枠：12週、24週、48週
|
12週、24週、48週
|
|
|
12週、24週、48週の赤血球沈降速度（ESR）値の比較
時間枠：12週、24週、48週
|
12週、24週、48週
|
|
|
12週、24週、48週におけるC反応性タンパク質（CRP）の値の比較
時間枠：12週、24週、48週
|
12週、24週、48週
|
|
|
24週目と48週目のEuroQol-5次元（EQ5D）スコアの比較
時間枠：24週と48週
|
24週と48週
|
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12、24、および 48 週で 1 以下の PD スコア (44 関節数) を達成した患者の比較
時間枠：12週、24週、48週
|
12週、24週、48週
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Comparison of value of VAS (Visual Analogue Scale) pain at weeks 12, 24 and 48
時間枠：12, 24 and 48 weeks
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Range: 0, better outcome - 100, worse outcome |
12, 24 and 48 weeks
|
|
Comparison of value of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity at weeks 12, 24 and 48
時間枠：12, 24 and 48 weeks
|
Range: 0, better outcome - 100, worse outcome |
12, 24 and 48 weeks
|
|
Comparison of value of VAS (Visual Analogue Scale) Physician Global Assessment of Disease Activity at weeks 12, 24 and 48
時間枠：12, 24 and 48 weeks
|
Range: 0, better outcome - 100, worse outcome |
12, 24 and 48 weeks
|
|
Comparison of Health assessment questionnaire (HAQ) score at week 24 and 48
時間枠：24 and 48 weeks
|
Range: 0, better outcome - 3, worse outcome |
24 and 48 weeks
|
|
Comparison of Rheumatoid Arthritis Impact of Disease (RAID) score at week 24 and 48
時間枠：24 and 48 weeks
|
Range: 0, better outcome - 10, worse outcome |
24 and 48 weeks
|
|
Comparison of Fatigue Assessment Scale (FAS) score at week 24 and 48
時間枠：24 and 48 weeks
|
Range: 10, better outcome - 50, worse outcome |
24 and 48 weeks
|
|
Comparison of the trend of VAS (Visual Analogue Scale) pain across all study visits
時間枠：48 weeks
|
Absolute and relative change of parameter with respect to the baseline and between different visits |
48 weeks
|
|
Comparison of the trend of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity across all study visits
時間枠：48 weeks
|
Absolute and relative change of parameter with respect to the baseline and between different visits |
48 weeks
|
|
Comparison of the trend of Health assessment questionnaire (HAQ) score across all study visits
時間枠：48 weeks
|
Absolute and relative change of score with respect to the baseline and between different visits |
48 weeks
|
|
Comparison of the trend of Rheumatoid Arthritis Impact of Disease (RAID) score across all study visits
時間枠：48 weeks
|
Absolute and relative change of score with respect to the baseline and between different visits |
48 weeks
|
|
Comparison of the trend of Fatigue Assessment Scale (FAS) score across all study visits
時間枠：48 weeks
|
Absolute and relative change of score with respect to the baseline and between different visits |
48 weeks
|
|
Comparison of the trend of EuroQol-5 dimensions (EQ5D) score across all study visits
時間枠：48 weeks
|
Absolute and relative change of score with respect to the baseline and between different visits |
48 weeks
|
|
Comparison of the differences in the Sharp van der Heijde Score from baseline to week 48
時間枠：48 weeks
|
Range: 0, better outcome - 448, worse outcome |
48 weeks
|
|
Comparison of direct medical costs of treatment arms from baseline to week 24 and 48
時間枠：24 and 48 weeks
|
Measurement: Incremental cost-effectiveness ratio (ICER) |
24 and 48 weeks
|
|
Analysis regarding predictors of low disease activity or remission at 12, 24 and 48 weeks in patients treated with ≥1bDMARD as compared to those who receive pain therapy
時間枠：12, 24 and 48 weeks
|
Investigated predictors: baseline erythrocyte sedimentation rate, baseline C reactive protein, baseline ultrasound score (EULAR-OMERACT combined score) |
12, 24 and 48 weeks
|
協力者と研究者
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
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