Comparing the Efficacy of Tetrandrine Combined With Methotrexate and Methotrexate Alone in the Treatment of Rheumatoid arthritis---a Randomized, Double-blinded, Placebo-controlled, Multicenter Study
试验速览
- 阶段
- 不适用
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Proportion of Participants Achieving American College of Rheumatology (ACR) 20
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of tetrandrine, compared with placebo in 12 week or 24 week in RA patients with inadequate response to methotrexate.
详细描述
The investigators designed a randomized, double-blinded, placebo-controlled, multicenter study. Adults with active rheumatoid arthritis and inadequate response to methotrexate will be enrolled, meeting the 1987 revised American College of Rheumatology (ACR) or 2010 ACR & European alliance of associations for rheumatology (EULAR) classification criteria. Two hundred forty patients at 18 to 65 years of age will be enrolled in the study, and be randomly assigned (in a 1:1 ratio) to one of the two arms (group1: tetrandrine 40mg tid for 24 weeks or group 2: placebo two tablets tid for 12 weeks, and then 40mg tid for 12 weeks). Follow-up visits will occur on weeks 4, 12 and 24. The end points were 20% improvement in American College of Rheumatology criteria (ACR20) in 12 week.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-65 years old.
- •fulfilled the 1987 revised American College of Rheumatology (ACR) or 2010 ACR/EULAR classification criteria for RA.
- •DAS28-ESR>3.
- •MTX 7.5-20mg/w for at least 12 weeks before screening and keep stable doses for at least 4 weeks.
- •Prednisone (≤10mg/d) or equivalent dose is allowed. However, the dose should be stable for at least 4 weeks before screening and should not increase during follow-up. If glucocorticoids are not used before screening, short- and intermediate-acting glucocorticoids should have been stopped at least 1 week and long-acting glucocorticoids should have been stopped at least 2 weeks.
排除标准
- •Allergic to the drugs involved in the study, or allergic to more than two kinds of food or drugs or pollen.
- •Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase.
- •Any history or complication of other autoimmune diseases other than Sjogren's syndrome or Hashimoto Thyroiditis.
- •Current active infections.
- •Tested positive for any of the following in the Screening Phase: HIV, hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis C virus antibody (HCV antibody), or history of AIDs.
- •Females of childbearing or breastfeeding.
- •Presence of any unstable cardiovascular disease (including congestive heart failure with NYHA class III or IV, unstable angina pectoris, history of myocardial infarction within one year), and the presence of conditions that can lead to QTc prolongation or arrhythmia.
- •Presence of progressive, uncontrolled cerebrovascular disease, hematopoietic, endocrine (including diabetes), respiratory (including interstitial pneumonia and pulmonary fibrosis) and other serious diseases and psychiatric diseases, or the investigator believes that participation in the study would place the subject at unacceptable risk.
- •History of malignancy.
- •Laboratory tests during screening：i. WBC<3.5×109/L，PLT<90×109/L， Hb<90g/L; ii. ALT or AST>1.5ULN; iii. Scr>ULN.
- •Use of iguratimod or disease-modifying antirheumatic drugs (DMARDs) other than MTX (such as leflunomide, sulfasalazine, hydroxychloroquine, D- penicillamine, azathioprine, cyclosporine, cyclophosphamide, Tripterygium, etc.) within 4 weeks before enrollment.
- •Use of traditional Chinese medicines for rheumatoid arthritis within 4 weeks before enrollment.
- •Use of b/tsDMARDs within 12 weeks.
- •History of alcohol and drug abuse.
- •The investigator or subinvestigator would compromise the participant's ability to safely complete the study.
- •Participate in other clinical trial within 3 months prior to screening.
研究组 & 干预措施
placebo
Placebo administered orally thrice daily through Week 12. Starting at Week 12, participants were given tetrandrine 40 milligram (mg) orally thrice daily through Week 24.
干预措施: Tetrandrine (Drug)
tetrandrine
tetrandrine administered 40milligram (mg) orally thrice daily through Week 24.
干预措施: Tetrandrine (Drug)
placebo
Placebo administered orally thrice daily through Week 12. Starting at Week 12, participants were given tetrandrine 40 milligram (mg) orally thrice daily through Week 24.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Participants Achieving American College of Rheumatology (ACR) 20
时间窗: week 12
The ACR20 was achieved if there was at least a 20% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
次要结局
- Proportion of Participants Achieving American College of Rheumatology (ACR) 20(week 4 and week 24)
- Proportion of Participants Achieving American College of Rheumatology (ACR) 50 and ACR70(week 12 and week 24)
- Rates of European League Against Rheumatism (EULAR) Response Using DAS28-CRP(week 12 and week 24)
- Change From Baseline in Pain VAS Score(Baseline, week 4, week 12 and week 24)
- Change From Baseline in Disease Activity Score 28 (DAS28)-CRP(Baseline, week 4, week 12 and week 24)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)(Baseline, week 4, week 12 and week 24)
- Change From Baseline in C-reactive Protein (CRP) Values(Baseline, week 4, week 12 and week 24)
- Change From Baseline to Week 24 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema.(Baseline and week 12)
- Change From Baseline in immune cells(Baseline, week 12 and week 24)
- Change From Baseline in Simplified Disease Activity Index (SDAI) Score(Baseline, week 4, week 12 and week 24)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score(Baseline, week 4, week 12 and week 24)