Evaluation of Desensitization Protocols in HLA-incompatible Kidney-transplant Candidates
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors.
研究概览
简要总结
Kidney transplantation is the best renal-replacement in the setting of end-stage renal disease. However, some transplant candidates have developed anti-HLA alloantibodies (human leukocyte antigen). When they are numerous and when their strength assessed by mean fluorescence intensity (MFI) is high it is very complicated to find-out a suitable kidney allograft against which the recipient has a negative cross-match. In such a case the only hope for the patient is desensitization therapy, whereby the treatment will decrease anti-HLA alloantibodies below a threshold, i.e. MFI < 3,000, enabling kidney transplantation without risking antibody-mediated rejection. Desensitization relies on i) apheresis technics in order to withdraw circulating anti-HLA antibodies, and ii) immunosuppression, i.e. rituximab or tocilizumab, targeting B-lymphocytes, and tacrolimus/mycophenolic acid/steroids targeting T-cells. The type of apheresis is guided by the pre-desensitization MFI of anti-HLA alloantibodies, e.g. double filtration plasmapheresis or semispecific immunoadsorption. Likely the choice between rituximab and tocilizumab depends also on predesensitization anti-HLA antibody MFIs. At the end of the desensitization process, the patient will be able to get a kidney transplant either from a live-donor or from a deceased donor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •Patients on the kidney transplant list, waiting for a first or repeat transplant
- •Presence of anti HLA antibodies either class I and/or II
- •Sensitized against a potential living donor or have been on the waiting list for at least 3 years and having no potential live-donor
- •Patients eligible for desensitization will receive either rituximab alone, or rituximab plus apheresis, or tocilizumab before rituximab
- •Normal recent (<6 months) cardiac workup
- •Vaccinated against pneumococcus and meningococcus B and C
- •Willingness of the patient to undergo the desensitization process and Express consent of the patient
- •for women of childbearing age, effective contraception or abstinence
- •Affiliated to a social security scheme or of such a scheme
排除标准
- •Active underlying infections or neoplasia
- •Pregnant women, parturient or breastfeeding
- •Subject in exclusion period of another study
- •Subject under administrative or judicial control
- •Subject who cannot be contacted in an emergency
- •Rituximab contra indication: hypersensitivity (to active substance or murine protein), active and severe infections, patients in a severely immunocompromised state, severe heart failure or severe, uncontrolled cardiac disease.
- •Tocilizumab contra indication: hypersensitivity, active and severe infections. Apheresis contra indication: active and severe infection, untreated or instable coagulation disorders, unstable coronary disease, recent stroke, hemodynamic instability.
研究组 & 干预措施
Desensitization with Tocilizumab and rituximab (MFI >15000)
干预措施: visits of tocilizumab injection (every 4 weeks, up to 5 visits) (Drug)
Desensitization with Tocilizumab and rituximab (MFI >15000)
干预措施: Rituximab 375 mg/m2 at Day-30 (Drug)
Desensitization with Tocilizumab and rituximab (MFI >15000)
干预措施: Rituximab 375 mg/m2 at Day-15 (only for donors living) (Drug)
Desensitization with Tocilizumab and rituximab (MFI >15000)
干预措施: Transplant Day-0 (Other)
Desensitization with Rituximab only (MFI<15000)
干预措施: Rituximab 375 mg/m2 at Day-30 (Drug)
Desensitization with Rituximab only (MFI<15000)
干预措施: Rituximab 375 mg/m2 at Day-15 (only for donors living) (Drug)
Desensitization with Rituximab only (MFI<15000)
干预措施: Transplant Day-0 (Other)
结局指标
主要结局
Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors.
时间窗: at day 1 start of desensitization, at day 0 of Graft
Decrease of MFI for highest donor-specific alloantibody (DSA) between start and end of desensitization for every patient in each category
次要结局
- Desensitization efficacy with regards to DSA decrease and kidney transplantation(Day-198, at day-30 Graft, at day-15, at day0 of Graft,)
- impairment of DSA synthesis(Day-198, at day-30 Graft, at day-15, at day0 of Graft,)
- Impairment of immune response(Day-198, at day-30 Graft, at day-15, at day0 of Graft,)
- Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability)(Day-198, at day-30 Graft, at day-15)