A 2 Year Prospective Multicentre Randomised Controlled Trial Comparing Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 400
- 试验地点
- 17
- 主要终点
- Remission According to DAS28-CRP at Week 52
研究概览
简要总结
The Combinatietherapie Bij Reumatoide Artritis (CoBRA) trial was a milestone in the development of the present treatment paradigm for Rheumatoid Arthritis (RA). This study introduced the principle of fast remission induction by means of a combination of standard Disease Modifying AntiRheumatic Drugs (DMARDs) and a step down bridge therapy with high dose glucocorticoids in early Rheumatoid Arthritis.
The purpose of the present study is to compare different combinations of traditional DMARDs and glucocorticoids, based on the original CoBRA protocol, for treatment of early Rheumatoid Arthritis.
Besides the efficacy and effectiveness of these strategies, patient centered outcomes and potential implementation problems of such treatment strategies are evaluated.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of RA as defined by the 1987 or 2010 revised American College of Rheumatology (ACR) criteria
- •Early RA (less than 1 year)
- •Use a reliable method of contraception for women of childbearing potential
- •Able and willing to give written informed consent and participate in the study
排除标准
- •Previous treatment with DMARDs
- •Previous treatment with oral corticosteroids at a dosage of more than 10 milligrams (mg) prednisone within 4 weeks before baseline
- •Previous treatment with oral corticosteroids at a dosage equal to or less than 10 mg prednisone within 2 weeks before baseline
- •Previous treatment with oral corticosteroids for more than 4 weeks
- •Previous treatment with Intra Articular corticosteroids within 4 weeks before baseline
- •Previous treatment with an investigational drug for the treatment or prevention of RA
- •Contraindications for corticosteroids
- •Contraindications for DMARDs
- •Psoriatic Arthritis
- •Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
- •Pregnancy, breastfeeding or no use of a reliable method of contraception
- •Alcohol or drug abuse
研究组 & 干预措施
CoBRA classic high risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Sulfasalazine 2g tablet by mouth, daily for 40 weeks
- Prednisone tablet by mouth, weekly step down scheme 60 - 40 - 25 - 20 - 15 - 10 mg daily for 6 weeks, followed by 7.5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Methotrexate (Drug)
CoBRA classic high risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Sulfasalazine 2g tablet by mouth, daily for 40 weeks
- Prednisone tablet by mouth, weekly step down scheme 60 - 40 - 25 - 20 - 15 - 10 mg daily for 6 weeks, followed by 7.5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Sulfasalazine (Drug)
CoBRA classic high risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Sulfasalazine 2g tablet by mouth, daily for 40 weeks
- Prednisone tablet by mouth, weekly step down scheme 60 - 40 - 25 - 20 - 15 - 10 mg daily for 6 weeks, followed by 7.5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Prednisone (Drug)
CoBRA slim high risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Methotrexate (Drug)
CoBRA slim high risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Prednisone (Drug)
CoBRA avant-garde high risk group
- Methotrexate 15mg tablet by mouth, weekly for 40 weeks (continued for entire trial if randomized to Methotrexate monotherapy at week 40)
- Leflunomide 10mg tablet by mouth, daily for 40 weeks (continued for entire trial if randomized to Leflunomide monotherapy at week 40)
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Methotrexate (Drug)
CoBRA avant-garde high risk group
- Methotrexate 15mg tablet by mouth, weekly for 40 weeks (continued for entire trial if randomized to Methotrexate monotherapy at week 40)
- Leflunomide 10mg tablet by mouth, daily for 40 weeks (continued for entire trial if randomized to Leflunomide monotherapy at week 40)
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Leflunomide (Drug)
CoBRA avant-garde high risk group
- Methotrexate 15mg tablet by mouth, weekly for 40 weeks (continued for entire trial if randomized to Methotrexate monotherapy at week 40)
- Leflunomide 10mg tablet by mouth, daily for 40 weeks (continued for entire trial if randomized to Leflunomide monotherapy at week 40)
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Prednisone (Drug)
CoBRA slim low risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Methotrexate (Drug)
CoBRA slim low risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- Prednisone tablet by mouth, weekly step down scheme 30 - 20 - 12.5 - 10 - 7.5 mg daily for 5 weeks, followed by 5mg daily till week 28, then further tapered down to stop at week 32
干预措施: Prednisone (Drug)
Tight Step Up low risk group
- Methotrexate 15mg tablet by mouth, weekly for entire trial
- No oral steroids allowed during the first year of the trial
干预措施: Methotrexate (Drug)
结局指标
主要结局
Remission According to DAS28-CRP at Week 52
时间窗: week 52
Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 52. (co-primary end point) DAS28-CRP is calculated with the following formula : 0.56\*SQRT TJC28+0.28\*SQRT SJC28+0.36\*ln (CRP+1)+0.014\*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS). A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity.
Remission According to DAS28-CRP at Week 104
时间窗: week 104
Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 104. (co-primary endpoints) DAS28-CRP is calculated with the following formula : 0.56\*SQRT TJC28+0.28\*SQRT SJC28+0.36\*ln (CRP+1)+0.014\*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS). A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity.
Remission According to DAS28-CRP at Week 16
时间窗: week 16
Number of patients in remission according to DAS28-CRP (Disease Activity Score based on 28 joint count and C-reactive Protein) at week 16. DAS28-CRP is calculated with the following formula : 0.56\*SQRT TJC28+0.28\*SQRT SJC28+0.36\*ln (CRP+1)+0.014\*GH+0.96 in which TJC is the tender joint count, SJC the Swollen Joint Count and GH the general health estimated by the patient on a Visual Analogue Scale (VAS). A value below 2.6 is indicating remission, below or equal to 3.2 low disease activity, between 3.2 and 5.1 moderate disease activity and above 5.1 high disease activity.
次要结局
- Clinically Significant Change in HAQ Score(Baseline-week104)
- Remission According to SDAI at Week 104(week 104)
- Remission According to SDAI (Simple Disease Activity Index) at Week 16(week 16)
- Remission According to SDAI at Week 52(week 52)
研究者
P. Verschueren
Prof. Dr.
Universitaire Ziekenhuizen KU Leuven