Mechanistic Evaluation of Treatments for Acute Antibody-Mediated Rejection of the Kidney Transplant
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 170
- 主要终点
- Allograft Survival as assessed by statistical model
研究概览
简要总结
The best treatment for kidney failure is a kidney transplant, but a transplanted kidney only works for about 10 to 15 years on average. One of the reasons that a transplanted kidney can stop working is that the body develops antibodies against it. Antibodies are proteins produced by the body to fight infections. They play a vital role in dealing with infection but in some transplant patients they can 'fight' the organ, meaning it could stop working. This is called acute antibody-mediated rejection (AAMR). A patient experiencing AAMR can be treated to extend the life of the transplanted kidney, but the chances of the kidney still working 4 years later are reduced. There is currently a clinical trial for UK kidney transplant patients who develop AAMR, called TAR:GET-1. Patients participating in TAR:GET-1 will either receive the standard treatment that is currently given in this situation, or the standard treatment with the addition of rituximab. TAR:GET-1 will answer the question: does adding rituximab to standard treatment lengthen the life of a kidney transplant? A second, sub-study is being proposed of the patients enrolled in TAR:GET-1, that will use the existing blood and biopsy samples already taken during TAR:GET-1 plus an optional extra biopsy of the kidney transplant, to improve our understanding of how the treatments of AAMR work. Patients enrolled in TAR:GET-1 will have had a blood test and biopsy of the transplanted kidney to establish the diagnosis of AAMR. They will also have had further blood tests after treatment, and may also have further biopsies taken if their clinician needs these as part of normal care. Material left over in these samples can be used to analyse how treatment works. In addition, patients will be asked if they agree to an extra biopsy of the transplanted kidney 6 months after the treatment begins. These samples will be analysed at a deeper level than would normally be done, looking at the antibodies and biopsies in detail to answer 2 key questions: 1) Can the unique characteristics noted in an individual patient's antibodies and biopsy predict whether a kidney transplant will be lost as a result of AAMR?; 2) Can we tell treatment is working by looking at the changes in a patient's antibodies and biopsies before and after treatment? The answers to these questions will help us understand AAMR and how its treatments work, and potentially improve our ability to select the right treatment for the right patients.
详细描述
Design: Prospective observational study of patients enrolled in TAR:GET-1
Objectives: TAR-GET-1 (starting in 2019) is a multi-centre UK clinical trial that will compare standard of care (SOC) treatment of Acute Antibody-Mediated Rejection of the Kidney Transplant (AAMR) to standard of care plus rituximab (SOCR). This trial presents a rare opportunity to investigate the mechanisms of action of treatments (including rituximab) in AAMR. The rationale for using rituximab is the depletion of CD20-positive precursors to antibody-producing cells. However, rituximab has effects on other B cell subtypes and not all studies have shown antibody level reductions. Furthermore, AAMR is a heterogeneous disease, as defined by variability in mechanistic markers of AAMR in blood (B cell and antibody characteristics) and in transplant biopsies (histological features and gene expression).
The objectives of this study are:
- To investigate how treatment with rituximab affects these mechanistic markers, by comparing SOC to SOCR
- To predict treatment benefit early, by analysing the effect of treatment on the mechanistic markers
Methodology: In patients enrolled in TAR:GET-1 (n=170), mechanistic markers will be analysed with established proof of concept (B cell and antibody characteristics, histological and transcriptional markers in the biopsy) at baseline and on follow-up, making use of clinical data, surplus diagnostic material from TAR:GET-1, and material from optional extra blood samples for research taken as part of TAR:GET-1, at 3,6 and 12 months. An optional protocol biopsy at 6 months post treatment will also be offered.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients enrolled in TAR:GET-1 Signed informed consent prior to any study specific procedures.
排除标准
- 未提供
研究组 & 干预措施
Rituximab + SOC (SOCR)
See NCT03994783
干预措施: Rituximab (Drug)
结局指标
主要结局
Allograft Survival as assessed by statistical model
时间窗: 4 years
Statistical model measuring allograft survival as defined as duration from the date of randomisation to the date of eGFR ≤15 mL/min/1.72 m2, or the date of renal replacement therapy (date of starting dialysis dependency, transplantation etc), whichever occurs first.
次要结局
未报告次要终点