Musculoskeletal Ultrasound in Predicting Early Dose Titration With Tocilizumab (RASTS)
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
-
-
California
-
Los Angeles、California、美国、90095
- UCLA David Geffen School of Medicine, Division of Rheumatology
-
-
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
Inclusion Criteria
Patients must have rheumatoid arthritis. Patients will be included in the trial based on the following criteria:
- Patient must meet 1987 American College of Rheumatology (ACR) criteria,
- Age > 18 years of age,
- Baseline DAS28/ESR>4.4,
Stable concomitant DMARDs for more than 1 month (methotrexate, leflunomide, plaquenil, sulfasalazine, or no DMARDs). However, if the patient is not on DMARD, history of DMARD use required.
- If not on DMARD (and the patient satisfies the above statement), the patient can opt for monotherapy with tocilizumab or combination therapy OR
- If on biologic monotherapy, can opt for monotherapy with tocilizumab or DMARD combination therapy (ie. patients cannot be on biologic with TCZ)
6) Power Doppler score of >10 at screening.
General Medical Concerns:
- Normal organ function, except if abnormal due to the disease under investigation
- Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
- Subject has provided written informed consent.
Exclusion Criteria
A patient will be excluded if the answer to any of the following statements is "yes".
General:
Major surgery (including joint surgery) within 8 weeks prior to baseline or planned major surgery within 6 months after baseline.
Excluded Previous or Concomitant Therapy:
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of baseline.
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3.
- Previous treatment with anti-CD19 and anti-CD20 within 6 months of start of the study.
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.
- Previous treatment with TCZ.
- Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
Use of prednisone > 10mg at baseline.
Exclusions for General Safety:
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)
- Current liver disease as determined by principal investigator unless related to primary disease under investigation
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of baseline or oral antibiotics within 2 weeks prior to baseline.
- Active Tuberculosis (TB) requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patients treated for tuberculosis with no recurrence in 3 years are permitted.
- Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
- Evidence of active malignant disease, malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 5 years.
- Pregnant women or nursing (breast feeding) mothers.
- Patients with reproductive potential not willing to use an effective method of contraception.
- History of alcohol, drug or chemical abuse within 1 year prior to screening.
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.
- Patients with lack of peripheral venous access.
Body weight of > 150 kg.
Laboratory Exclusion criteria (at screening):
- Serum creatinine > 1.6 mg/dL (141 µmol/L) in female patients and > 1.9 mg/dL (168 µmol/L) in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are >30.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
- Total Bilirubin > ULN
- Platelet count < 100 x 109/L (100,000/mm3)
- Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
- White Blood Cells < 3.0 x 109/L (3000/mm3)
- Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)
- Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)
- Positive Hepatitis BsAg, or Hepatitis C antibody
- HIV positive
学习计划
研究是如何设计的?
设计细节
- 主要用途:其他
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
其他:Tocilizumab
All subjects will receive tocilizumab.
|
All subjects will start at 4mg/kg.
After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.
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 |
---|---|---|
Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
大体时间:Baseline, 3 Month
|
34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Power Doppler scores. This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level. |
Baseline, 3 Month
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Baseline to Month 6 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
大体时间:Baseline, 6 Month
|
34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Power Doppler scores. This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level. |
Baseline, 6 Month
|
Baseline to Month 3 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints
大体时间:Baseline, 3 Month
|
34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Synovial Hypertrophy Scores. This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for GSUS represents more severe disease level. |
Baseline, 3 Month
|
Baseline to Month 6 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints
大体时间:Baseline, 6 Month
|
34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Synovial Hypertrophy Scores. This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for GSUS represents more severe disease level. |
Baseline, 6 Month
|
Baseline to Month 3 Change in DAS28/ESR
大体时间:Baseline, 3 month
|
28 joints will be evaluated for Tender Joint Count (TJC) and Swollen Joint Count (SJC) as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 3 Month Disease Activity Score (DAS) scores. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease. |
Baseline, 3 month
|
Baseline to Month 6 Change in DAS28/ESR
大体时间:Baseline, 6 Month
|
28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 6 Month DAS scores. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease. |
Baseline, 6 Month
|
Baseline to Month 3 Change in CDAI
大体时间:Baseline, 3 month
|
28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 3 Month CDAI scores. The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity. |
Baseline, 3 month
|
Baseline to Month 6 Change in CDAI
大体时间:Baseline, 6 Month
|
28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 6 Month CDAI scores. The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity. |
Baseline, 6 Month
|
合作者和调查者
合作者
调查人员
- 首席研究员:Veena Ranganath, MD, MS、UCLA David Geffen School of Medicine, Division of Rheumatology
出版物和有用的链接
一般刊物
- Morris NT, Brook J, Ben-Artzi A, Martin W, Kermani TA, Avedikian-Tatosyan L, Karpouzas G, Nagam H, Navarro G, Choi S, Taylor MB, Elashoff D, Kaeley GS, Ranganath VK. Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients. Clin Rheumatol. 2021 Dec;40(12):5055-5065. doi: 10.1007/s10067-021-05857-7. Epub 2021 Jul 16.
- Kuo D, Morris NT, Kaeley GS, Ben-Artzi A, Brook J, Elashoff DA, Ranganath VK. Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy. Clin Rheumatol. 2021 Mar;40(3):1077-1084. doi: 10.1007/s10067-020-05340-9. Epub 2020 Aug 15.
- Choate EA, Kaeley GS, Brook J, Altman RD, FitzGerald JD, Floegel-Shetty AR, Elashoff DA, Ranganath VK. Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoid arthritis patients. BMC Rheumatol. 2020 Feb 3;4:8. doi: 10.1186/s41927-019-0107-2. eCollection 2020.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
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
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
Tocilizumab的临床试验
-
University Hospital for Infectious Diseases, Croatia未知
-
Hoffmann-La Roche完全的
-
Hoffmann-La Roche完全的类风湿关节炎法国, 德国, 意大利, 西班牙, 英国, 香港, 美国, 哥伦比亚, 巴西, 加拿大, 新西兰, 南非, 菲律宾, 俄罗斯联邦, 泰国, 新加坡, 保加利亚, 墨西哥, 澳大利亚, 立陶宛, 波兰, 阿根廷, 罗马尼亚, 波多黎各, 危地马拉, 秘鲁
-
Azienda Unità Sanitaria Locale Reggio Emilia主动,不招人
-
Hoffmann-La Roche完全的类风湿关节炎美国, 巴西, 英国, 加拿大, 阿根廷, 墨西哥, 奥地利, 以色列, 哥伦比亚, 秘鲁, 俄罗斯联邦, 菲律宾, 波多黎各, 德国, 希腊, 波兰, 西班牙, 法国, 新加坡, 中国, 南非, 匈牙利, 丹麦, 芬兰, 瑞典, 香港, 澳大利亚, 危地马拉, 爱尔兰, 意大利, 马其顿,前南斯拉夫共和国, 新西兰, 巴拿马, 葡萄牙, 泰国, 火鸡
-
Fondazione IRCCS Ca' Granda, Ospedale Maggiore...Azienda Ospedaliero, Universitaria Pisana; Istituto Auxologico Italiano; Azienda Ospedaliera "Sant... 和其他合作者招聘中
-
Damanhour UniversityPrincipal Investigator Sahar El-Haggar, Prof Clinical pharmacy Department- Tanta University; Principal Investigator Sahar Hegazy, Prof Clinical pharmacy Department- Tanta University 和其他合作者招聘中