Ultrasound to Guide Treatment Decisions in Patients With Rheumatoid Arthritis According to a T2T Approach
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 158
- 试验地点
- 2
- 主要终点
- Non-inferiority of ultrasound-based decision strategy compared to clinically-based strategy.
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Non-inferiority of ultrasound-based decision strategy compared to clinically-based strategy.
时间窗: 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.
次要结局
- Comparison of the proportion of patients in low disease activity and MCII or remission according to ACR/EULAR index-based remission criteria at week 12 and 48(12 and 48 weeks)
- Comparison of the proportion of patients in remission according to DAS-28 (DAS-28 ≤2.6) or SDAI (≤3.3) at week 12, 24 and 48(12, 24 and 48 weeks)
- Comparison of value of tender joints count at weeks 12, 24 and 48(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(12, 24 and 48 weeks)
- Comparison of value of erythrocyte sedimentation rate (ESR) at weeks 12, 24 and 48(12, 24 and 48 weeks)
- Comparison of Fatigue Assessment Scale (FAS) score at week 24 and 48(24 and 48 weeks)
- Comparison of the trend of Health assessment questionnaire (HAQ) score across all study visits(48 weeks)
- Comparison of Rheumatoid Arthritis Impact of Disease (RAID) score at week 24 and 48(24 and 48 weeks)
- Comparison of value of VAS (Visual Analogue Scale) pain at weeks 12, 24 and 48(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(12, 24 and 48 weeks)
- Comparison of EuroQol-5 dimensions (EQ5D) score at week 24 and 48(24 and 48 weeks)
- Comparison of the differences in the Sharp van der Heijde Score from baseline to week 48(48 weeks)
- Comparison of direct medical costs of treatment arms from baseline to week 24 and 48(24 and 48 weeks)
- Comparison of the proportion of patients in remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission, respectively) at week 12, 24 and 48(12, 24 and 48 weeks)
- Comparison of value of swollen joints counts at weeks 12, 24 and 48(12, 24 and 48 weeks)
- Comparison of value of C reactive protein (CRP) at weeks 12, 24 and 48(12, 24 and 48 weeks)
- Comparison of Health assessment questionnaire (HAQ) score at week 24 and 48(24 and 48 weeks)
- Comparison of the trend of VAS (Visual Analogue Scale) Patient Global Assessment of Disease Activity across all study visits(48 weeks)
- Comparison of the trend of Rheumatoid Arthritis Impact of Disease (RAID) score across all study visits(48 weeks)
- Comparison of the trend of EuroQol-5 dimensions (EQ5D) score across all study visits(48 weeks)
- Comparison of patients achieving a PD score of ≤1 (44-joint count) at weeks 12, 24 and 48(12, 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(12, 24 and 48 weeks)
- Comparison of the trend of VAS (Visual Analogue Scale) pain across all study visits(48 weeks)
- Comparison of the trend of Fatigue Assessment Scale (FAS) score across all study visits(48 weeks)