A Multicenter Randomized Controlled Trial of Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of Idiopathic Membranous Nephropathy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 7
- 主要终点
- complete remission (CR) or partial remission (PR) at 24 month
研究概览
简要总结
The primary objective of this study is to determine whether or not cyclosporine (CsA) combined with RTX is more effective than RTX alone in the treatment of idiopathic membranous nephropathy (iMN).
详细描述
To date, the first-line immunosuppressive therapy of iMN includes corticosteroids combined with cyclophosphamide or Rituximab (RTX) which has been used more and more widely due to superior safety profiles. But the long term remission rate of RTX monotherapy is only 60% and it takes effect relatively slowly.
2 pilot studies reported that the combination therapy of cyclosporine (CsA) and RTX had better efficacy for inducing remission for iMN, with the long term remission rate up to 85%. CsA and RTX may have synergistic effect in the treatment of iMN because they have different time of action and different effects on the immune system and podocytes.
Based on the previous rationale, the investigators designed this trial to determine whether combination of CsA and RTX is more effective than RTX alone in the treatment of iMN.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •idiopathic MN with or without diagnostic biopsy
- •Female, must be post-menopausal, sterile or have effective method of contraception
- •must be off steroid or mycophenolate mofetil for >1 month and alkylating agents for > 6 months
- •Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥3 months prior to randomization with controlled blood pressure or if patients is intolerant to ACEI/ARB
- •proteinuria ≥4g/24h using the average from two 24-hour urine samples collected within 2 weeks of each other, and decreased ≤50% from baseline.
- •estimated glomerular filtration rate (eGFR) ≥40ml/min/1.73m2
排除标准
- •presence of active infection or a secondary cause of MN
- •diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
- •pregnancy or breast feeding
- •history of resistance to CsA or other calcineurin inhibitors(CNI), RTX or alkylating agents.
- •Patients who previously achieved remission after treatment of CNI, RTX or alkylating agents but relapsed off CNI after 3 months, or relapsed off RTX or alkylating agents after 6 months, are eligible.
研究组 & 干预措施
Rituximab monotherapy
Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to the CD19+ B cells count.
干预措施: Rituximab (Drug)
Rituximab combined with cyclosporine
Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to CD19+ B cells count.
cyclosporine (CsA) will be started at a dose of 3mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Doses of CsA will be adjusted according to the blood levels of CsA. CsA will be tapered after 6 months and discontinued over a 3 month period.
干预措施: Rituximab (Drug)
Rituximab combined with cyclosporine
Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to CD19+ B cells count.
cyclosporine (CsA) will be started at a dose of 3mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Doses of CsA will be adjusted according to the blood levels of CsA. CsA will be tapered after 6 months and discontinued over a 3 month period.
干预措施: cyclosporine (Drug)
结局指标
主要结局
complete remission (CR) or partial remission (PR) at 24 month
时间窗: 24 months after randomization
complete or partial remission at 24 month. complete remission is defined as urine protein≤0.5g/24h and serum albumin≥3.5g/dl. Partial remission is defined as reduction in baseline urine protein ≥50% plus urine protein≤3.5g/24h but \>0.5g/24h
次要结局
- complete remission (CR) or partial remission (PR) on 6 month, 12 month, 18 month(6, 12, 18 months after randomization)
- complete remission (CR) on 6, 12, 18, 24 month(6, 12, 18, 24 months after randomization)
- Time to complete remission (CR) or partial remission (PR)(from date of randomization until the date of first remission, assessed up to 24 months)
- Change of estimated glomerular filtration rate (eGFR)(24 months)
- Serum creatinine increase≥50 percent from baseline(24 months)
- Proportion of patients with relapse(12，18，24 months)
- Anti-PLA2R titer(baseline and 3, 6, 9, 12, 18, 24 months)
- The number of CD19+B cells(baseline and 3, 6, 9, 12, 18, 24 months)
- Adverse events(through study completion until 24 months)
- Quality of life measured by kidney disease and quality of life (KDQOL-36)(baseline, 12 and 24 month)