A Prospective Randomized Study on the Efficacy and Safety of the Prophylactic Use of Rituximab, Added to Standard Immunosuppressive Treatment in Comparison With Standard Immunosuppressive Treatment Alone in Renal Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- Incidence and severity of biopsy-confirmed acute rejection
研究概览
简要总结
Our standard immunosuppressive treatment after renal transplantation is a combination of tacrolimus, mycophenolate mofetil, and prednisolone. With this regimen the incidence of acute rejection within the first six months after transplantation has dropped to about 20%. The main challenge at present remains to improve long-term outcome by preventing chronic allograft nephropathy (CAN). Since acute rejection is a strong predictor of CAN, a further decrease in the incidence of acute rejection can improve the long-term graft survival. Current strategies to prevent rejection are mainly directed at alloreactive T cells. Recently, the attention for the role of antibodies in the pathogenesis of acute rejection has increased. In addition, anti-B cell therapy was shown to be effective in diseases that were considered to be mainly T cell driven, like rheumatoid arthritis. In the latter case it has been suggested that anti-B cell antibodies may impair the antigen presenting function of B cells. We therefore decided to investigate the effectiveness and safety of the anti-B cell monoclonal antibody rituximab for prophylaxis of acute rejection after renal transplantation.
Study design: Double-blind, placebo controlled intervention study. One group receives a single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation, and the other group receives a placebo infusion.
Primary Objective:
To determine the incidence and severity of biopsy-confirmed acute rejection within the first six months after transplantation.
Secondary Outcomes:
- Renal function as estimated by the endogenous creatinine clearance at 6 months
- Occurrence of chronic allograft nephropathy at 6 months
- Cumulative incidence of infections and malignancies at 6 months
- Medical costs during the first 6 months after transplantation
- Patient and graft survival
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Renal transplant recipients
- •Signed, dated, and witnessed IRB approved informed consent
排除标准
- •Pregnancy
- •Living donor, who is HLA identical.
- •Hemolytic uremic syndrome as original kidney disease.
- •Focal segmental glomerulosclerosis that had recurred in a previous graft.
- •More than two previously failed grafts and/or PRA > 85%.
- •Previous treatment with anti-CD20 antibodies.
- •Diabetes mellitus that is currently not treated with insulin.
- •Total white blood cell count <3,000/mm3 or platelet count <75,000/mm
- •Active infection with hepatitis B, hepatitis C, or HIV.
- •History of tuberculosis
研究组 & 干预措施
1
Rituximab
干预措施: Rituximab (Drug)
2
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of biopsy-confirmed acute rejection
时间窗: First six months after transplantation
次要结局
- Occurrence of chronic allograft nephropathy(First 6 months after transplantation)
- Patient and graft survival(First six months after transplantation)
- Renal function as estimated by the endogenous creatinine clearance(6 months after transplantation)
- Cumulative incidence of infections and malignancies(First 6 months after transplantation)