Randomized Controlled Multicenter Trial to Evaluate the Efficacy and Safety of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 6
- 主要终点
- compare levels of eGFR measured by CKD-EPI equation in both arms
研究概览
简要总结
The investigator hypothesizes that the combined use of (1) Donor-derived cell-free DNA (dd-cfDNA) in peripheral blood predicting anti-donor immunological activation or quiescence (2) interactive and actionable data analytics delivered at the bedside will promote safe clinical follow-up of kidney transplant patients with less need for invasive biopsy and less induced risk surveillance by allograft protocol biopsies to assess allograft rejection in clinically stable kidney transplant patients.
In addition, the evaluation of the transcriptional changes in tissue samples in selected patients using automated processing of digital slide images and intragraft gene expression profiles will provide a better diagnosis of the rejection mechanisms to provide the best therapeutic approach as compared to current clinical practice.
We therefore propose a French, multicenter, prospective randomized trial comparing two strategies of follow-up: in the first group, a biopsy is performed at M3, M12 and for clinical indication whenever considered necessary by the clinician during the first 18 months of follow-up after transplant. In the second group, patients will have the same follow-up as in the first group, but reports providing dd-cfDNA results and relevant medical parameters will be provided to the physician to help him in the decision to perform a biopsy or not.
详细描述
The main objective of the study is to assess whether the use of donor-derived cell-free DNA (dd-cfDNA) as an immunological biomarker combined with clinical data to decrease the number of allograft biopsies during the first 18 months after transplantation.
500 new transplanted patients in 6 French clinical transplant sites will be included in the prospective multicenter AI-CARE trial. Recruitment of patients will start on the day of transplantation (or 8 days before for transplantations with living donor) and data/samples collected at 3 months and 12 months after transplantation and during visits for clinical indication within the first 18 months of follow-up. Realization of all the acts for the research are representing the usual medical practice (Standard Of Care: SOC) except one additional blood sample for dd-cfDNA analyses that will be collected and analyzed specifically for the research. The paraffin-embedded core dedicated to SOC histology will be used for gene expression profiling and digital pathology imaging after SOC procedures.
Using the newest information derived from dd-cfDNA analyses combined with clinical data, dd-cfDNA will allow us to identify kidney transplant patients at low- and high-risk of rejection.
using non-invasive dd-cfDNA levels combined with clinical data, preventing unnecessary allograft biopsies which are invasive, with and present a potential risk of complications for the patients and costly burden to the healthcare
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 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
- •All men and women, age ≥18 years old.
- •Subject must be a recipient of a non-combined renal transplant from a deceased or living donor. It can be a re transplantation after a graft loss of function or graft rejection
- •Subject is willing and able to provide signed written informed consent and willing to comply with study procedures
- •Women of Childbearing Potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
排除标准
- •Subjects who are legally detained in an official institution or under legal protection
- •Any condition that, in the opinion of the investigator, might interfere with the patient 's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient
- •History of multi-organ transplant (interference with rejection natural history).
研究组 & 干预措施
Group II: dd-cfDNA-guided
Patients will follow a dd-cfDNA-guided strategy based on dd-cfDNA levels in the blood associated with relevant clinical data on the basis of its detection and prediction capacities for rejection at M3, M12 and during visits for clinical indication (5 CI visits maximum expected per patient between D0 and M18 to decide whether a biopsy is performed within the first 18 months of follow-up.
Patients will be classified in "High risk" and "Low risk" depending on the dd-cfDNA integrative report generated by PARCC INSERM UMR 970 after centralization of dd-cfDNA results.
If the patient is stratified into the "high-risk of rejection" subgroup, they can decide to perform the biopsy. In any case, the decision to perform the biopsy is left to the appreciation of the physician. They will report their awareness of the report's result to guide the act of biopsy in the eCRF.
like in Group I, the standard of care comprises two biopsy cores
干预措施: dd-cfDNA-guided (Biological)
结局指标
主要结局
compare levels of eGFR measured by CKD-EPI equation in both arms
时间窗: 18 months
Comparison of the levels of eGFR (mL/min/1.73m2) in both arms estimated by glomerular filtration rate (CKD-EPI eGFR) at 18 months' post-transplantation
次要结局
- compare EQ-5D-5L questionnaire answers between both group(18 months)
- modification of the immunosuppression treatment(18 months)
- graft survival rates(18 months)
- biopsy-proven rejections(18 months)
- incidence of death(18 months)
- probability of kidney allograft rejection measured by gene expression in the biopsy tissue(18 months)
- quantity of lesion patterns between both groups(18 months)
- compare health care expenses between both groups(18 months)
- compare the PREMs questionnaire answer in dd-cfDNA-guided group(18 months)
- compare the Generalised Anxiety Disorder Assessment (GAD-7 ) questionnaire answer between both group(18 months)
- compare the visual analyse scale ( VAS ) questionnaire answer between both group(18 months)