Evaluation of 2 Techniques of Apheresis to Desensitize ABO Incompatible Kidney Transplant Candidates: Double Filtration PlasmaPheresis (DFPP) vs Large Plasma Volume Specific ImmunoAdsorption
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Success rate
研究概览
简要总结
Kidney transplantation is the treatment of choice for end-stage renal disease. ABO incompatible (ABOi) living donor kidney transplantation is one of the best ways to expand the donors' pool. However, breaking the ABO barrier is possible only with a preconditioning regimen that includes 1) an immunosuppressive strategy using a B-cell depleting agent (rituximab), an induction therapy with polyclonal antibodies, and a maintenance triple immunosuppressive therapy based on calcineurin inhibitors, and 2) a desensitization protocol aiming to decrease the titer of isoagglutinins. For this purpose, several techniques of apheresis are available. To date, two main techniques used in clinical setting are the Double-Filtration PlasmaPheresis (DFPP) and the Antigen-Specific Immunoadsorption (SIA). DFPP permits the depletion of the selective plasma fraction containing Immunoglobulins, while limiting the need for plasma substitution. SIA enables to remove ABO antibodies without a major loss in essential plasma components. To date, no randomized study comparing DFPP and SIA exist. SIA is less often used because of its high cost. However, in order to reduce the number of SIA sessions and consequently its cost, large plasma volume sessions of SIA are performed. ABOi is dramatically more expensive than ABO compatible kidney transplantation. A large part of the difference in the cost is related to the apheresis technique.
Herein, the investigator proposes to describe the efficacy, the safety, and the cost of DFPP and SIA to desensitize ABO incompatible kidney transplant candidates.
详细描述
All recipients will receive an induction therapy with rituximab and polyclonal antibodies, as well as a maintenance therapy by tacrolimus, mycophenolic acid (switched for mTOR (Mechanistic target of rapamycin) inhibitors 1 month after the transplantation to avoid viral infections) and steroids.
The desensitization protocol will be based on the initial titer of isoagglutinin. All patients with an isoagglutinin titer between 1/8 and 1/128 will be included in this monocentric, open label study, and randomized between the DFPP arm (1 to 4 sessions according to the initial titer) and large-plasma SIA (1 to 2 sessions according to the titer). The effectiveness will be evaluated on the ability to obtain the targeted titer before transplantation (1/4) with less than 5 DFPP, or 2 large-plasma volume SIA.
All recipients will be followed for 6 months, and examined for surgical complications, rejection rate, and kidney function. All complications related to desensitization protocol will be reported. Moreover, all cost associated with these two apheresis techniques will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient eligible for living donor ABO incompatible kidney transplantation
- •Presenting an IsoAgglutinin immunoglobulin G titer (anti-A-B) between 1/8 and 1/128, before desensitization
- •Patient older than 18 years
- •Women of childbearing age must have a pregnancy test before starting the study and undergoing study. They must take an effective and acceptable method of contraception before starting the study and throughout the study period. Sexually active men should use a condom throughout the course of the study
- •Patient able to sign an informed consent form
- •Patient affiliated with a social security scheme
排除标准
- •Presence of anti-HLA (Human Leucocyte Antigens) allo-antibodies
- •Patient with comorbidities that prevent desensitization protocols
- •Women who are pregnant, or who may become pregnant or breastfeeding women
- •History of hypersensitivity related to a component of the apheresis membrane
- •Subjects under legal protection
- •Subjects participating in another interventional research protocol or in an exclusion period from another interventional research protocol
结局指标
主要结局
Success rate
时间窗: the day of transplantation
% of subjects with the targeted isoagglutinin titer (≤1/4) before transplantation with less than 5 DFPP sessions (for the DFPP arm) or 2 large plasma volume specific immunoadsorption sessions (for the specific immunoadsorption arm)
次要结局
- Surgical complication rate during the transplantation surgery(During the transplantation surgery)
- Differential cost-efficacy ratio of support for patients receiving a live donor kidney transplant Incompatible ABO and benefiting from a desensitization procedure(7 months)
- Surgical complication rate during the desensitization sessions(From the first desensitization session to the last one, assessed up to 10 days)
- Graft rejection rate 1 month after transplantation surgery(1 month after transplantation surgery)
- Graft rejection rate 3 months after transplantation surgery(3 months after transplantation surgery)
- Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) during the desensitization sessions(From the first desensitization session to the last one, assessed up to 10 days)
- Blood transfusion rate during the transplantation surgery(During the transplantation surgery)
- Thrombotic complication rate during the desensitization sessions(From the first desensitization session to the last one, assessed up to 10 days)
- Thrombotic complication rate 1 week after transplantation surgery(1 week after transplantation surgery)
- Rate of bleeding and/or hematoma on vascular access during the desensitization sessions(From the first desensitization session to the last one, assessed up to 10 days)
- Rate of hematoma occurrence during the transplantation surgery(During the transplantation surgery)
- Rate of occurrences of hemorrhage away from vascular access during the desensitization sessions(From the first desensitization session to the last one, assessed up to 10 days)
- Graft rejection rate 6 months after transplantation surgery(6 months after transplantation surgery)
- Renal function 6 months after transplantation surgery(6 months after transplantation surgery)
- Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) 1 week after transplantation surgery(1 week after transplantation surgery)
- Blood transfusion rate before transplantation(Before transplantation)
- Blood transfusion rate 1 week after transplantation surgery(1 week after transplantation surgery)
- Graft ablation rate 1 week after transplantation surgery(1 week after transplantation surgery)
- Occurrence rate of deep vein or graft vein thrombosis during the transplantation surgery(During the transplantation surgery)
- Need for dialysis session(s) 1 week after transplantation surgery(1 week after transplantation surgery)
- Complication rate on surgical area 1 week after transplantation surgery(1 week after transplantation surgery)
- Infectious complication rate 1 week after transplantation surgery(1 week after transplantation surgery)
- Renal function 1 month after transplantation surgery(1 month after transplantation surgery)
- Renal function 3 months after transplantation surgery(3 months after transplantation surgery)
- Change in hemostasis parameters from before the desensitization protocol to after(the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days))