Randomized Trial of Tofacitinib Versus Methotrexate for Maintenance Therapy in Granulomatosis With Polyangiitis
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Relapse rate (major or minor) at 12 months
研究概览
简要总结
The aim of this study is to identify the optimal maintenance therapy for granulomatosis with polyangiitis (GPA) by comparing the MTX (standard regimen) with Tofacitinib in terms of efficacy, i.e. in preventing relapses.
详细描述
Granulomatosis with polyangiitis (GPA), a systemic small-vessel vasculitis, could involve multiple tissues and organs. Remission of GPA can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent and remain a challenge. The optimal drug for maintenance treatment is not determined. Tofacitinib is a Jak inhibitor which has been proved to be effective in multiple inflammatory diseases such as rheumatoid arthritis. But the efficiency and safety of tofacitinib in treating GPA remains unclear yet. In the present randomized trial, the comparison of MTX (standard regimen) with Tofacitinib in terms of efficacy, i.e. in preventing relapses will be conducted.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed or relapsing Granulomatosis with polyangiitis met the criteria of 1990 ACR and 2012 Chapel Hill criteria
- •Patients in disease flare have achieved remission using a treatment combining corticosteroids and IV cyclophosphamide
- •Remission is defined as a Birmingham Vasculitis Activity/ Wegener's granulomatosis (BVAS/WG) score of 0 and receiving 10 mg/day of oral prednisone (or equivalent) at least 2 weeks
- •Age 18 to 75 years
- •Written informed consent obtained before taking part in the study
排除标准
- •Severe GPA defined as potentially organ- or life-threatening disease (i.e. alveolar haemorrhage, heart failure caused by myocarditis or pericarditis, progressive neurological symptoms, deaf, blindness, et al.)
- •Serum creatinine>120umol/L or proteinuria>1.0g/d
- •Failure to response after treatment with methotrexate or cyclophosphamide previously
- •Receipt of a JAKi therapy previously
- •Co-existence of another systemic autoimmune disease
- •Secondary vasculitis (following neoplastic disease, an infection or antithyroid drugs)
- •Malignancy or history of malignancy
- •Infection by HIV, HCV, HBV or tuberculosis
- •Severe uncontrolled cardiovascular, pulmonary, liver, gastrointestinal, endocrine, hematological, neurological, or psychiatric diseases that are not related to systemic vasculitis
- •Allergic to any of the medication (cyclophosphamide, corticosteroids, tofacitinib, methotrexate)
- •Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.5 x 109/L; Platelet count <100 x 109/L; Alanine transaminase or aspartate aminotransferase or total bilirubin>1.5 upper normal limit; Estimated glomerular filtration rate<60ml/min/1.73m2
- •Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect.
- •Incapacity or refusal to understand or sign the informed consent form.
- •Pregnancy, breastfeeding.
研究组 & 干预措施
Tofactitinib
partcipants would be given one tablet of tofacitinib (5mg per tablet), twice per day, the treatment duration will last 12 months during the whole follow-up period.
干预措施: Tofacitinib (Drug)
Methotrexate
partcipants would be given tablets of methotrexate (2.5mg per tablet) from the initial dose of 15mg (6 tablets) and add to the maximal and optimal dose of 20mg (8 tablets), once per week, the treatment duration will last 12 months during the whole follow-up period.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Relapse rate (major or minor) at 12 months
时间窗: From the enrollment to the the end of 12 month.
The major or minor relapse rate equals to the patients with relapse/ total participants ( A major relapse should be defined as the re-occurrence or new onset of potentially organ- or life-threatening disease activity that cannot be treated with an increase of GC alone and requires further escalation of treatment. All other relapses should be classified as minor.)
次要结局
- Cumulative dosage of corticosteroids(From the enrollment to the the end of 12 month.)
- Number of relapse(From the enrollment to the the end of 12 month.)
- Time to first relapse.(From the enrollment to the the end of 12 month.)
- Adverse events(From the enrollment to the the end of 12 month.)