Quantify the Benefits of Biomarkers in Routine Patient Care in Kidney Transplant Recipients

Study Overview
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Brief Summary
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The investigator hypothesize that the combined use of (1) non-invasive biomarkers 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 and induced risk surveillance by allograft protocol biopsies to assess allograft rejection in clinically stable kidney transplant patients. It is therefore proposed an European, multicenter, prospective randomized comparing two strategies of follow-up: in the first, biopsies are guided by biomarkers, in the second one, a routine biopsy is performed at M3. In both groups, a biopsy is performed at M12 and whenever considered necessary by the clinician.

Detailed Description
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The main objective of this study is to demonstrate the ability of use of non-invasive biomarkers to decrease the number of allograft biopsies during the first year after transplantation. 300 new transplanted patients in the 7 clinical transplant sites will be included in the prospective multicentre EU-TRAIN Impact study with centralized storage of samples in CHUN (blood mRNA), ICS (blood cellular assays), Saint -Louis Hospital (blood anti-HLA DSA, and non-HLA antibodies), INSERM (Biopsy mRNA). Recruitment of patients will start on the day of transplantation (d-8 for transplantation from living donors) and data/samples collected over the first year following transplantation. Realization of all the acts for the research are representing the usual medical practice (Standard Of Care: SOC) except six additional blood samples that will be collected and analyzed specifically for the research and additional analysis done specifically for the research on half of one of the two biopsy cores from the recipient. 3 additional blood samples from the living donor will also be collected and analyzed specifically for the research (timepoint of the sampling: anytime from 8 days to the day of transplant.

Official Title
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Randomized Controlled Multicentre Trial to Quantify the Benefits of Biomarkers in Routine Patient Care in Kidney Transplant Recipients EU-TRAIN IMPACT Trial

Conditions
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Renal Transplantation

Intervention / Treatment
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* Biological: biomarker-guided strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All men and women, age ≥18 years old. Subject must be a recipient of a single renal transplant from a deceased or living donor. 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. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL]. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of clinical trial Exclusion Criteria: Subject with Hepatitis B chronic infection and/or active infection by Hepatitis C virus (positive blood PCR result at the moment of transplant). Subjects with known human immunodeficiency virus (HIV) infection. Patients with active systemic infection that requires the continued use of antibiotics. Patients with neoplasia except localized skin cancer receiving appropriate treatment. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, women who are pregnant or breastfeeding or women with a positive pregnancy test on enrolment. Subjects who are legally detained in an official institution. Primary non-function or early graft loss due to mechanical/surgical complications. Death within the first 6 months after transplantation. 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a 12-month follow-up multicenter, randomized, biomarker strategy design trial, whereby kidney transplant patients will be randomized 1:1 at the time of transplantation in 2 study groups: Group I (routine group): Patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and a surveillance allograft biopsies performed at 3 and 12 months after transplantation (M3 and M12). Group II (biomarker guided follow-up): Patients will follow a biomarker-guided strategy based on specific non-invasive biomarkers as defined in EUTRAIN-1 study on the basis of its detection and prediction capacities for rejection at M3 to decide whether a biopsy is performed. At M12 a routine biopsy is performed. In both groups, a biopsy can be performed up on clinical decision if needed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: routine group<br>Patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and a surveillance allograft biopsies performed at 3 and 12 months after transplantation (M3 and M12). Visits with biopsies for clinical indication are left to the appreciation of the investigator | |
| Experimental: biomarker guided follow-up<br>Patients will follow a biomarker-guided strategy based on specific non-invasive biomarkers as defined in EUTRAIN-1 study on the basis of its detection and prediction capacities for rejection at M3 to decide whether a biopsy is performed. At M12 a routine biopsy is performed. Visits with biopsies for clinical indication are left to the appreciation of the investigator | Biological: biomarker-guided strategy<br>* Patients will follow a biomarker-guided strategy based on specific non-invasive biomarkers as defined in EUTRAIN-1 study on the basis of its detection and prediction capacities for rejection at M3 to decide whether a biopsy is performed. At M12 a routine biopsy is performed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of biopsies | comparison of the rate of biopsies performed during the first year in the Group of biomarkers guided biopsies vs. routine Group | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of immunosuppressant treatment modifications | Rate of immunosuppressant treatment modifications in both groups. | 12month | 
| Rate of complications due to performed biopsies | Rate of complications due to performed biopsies between both groups | 12month | 
| Type of biopsy-proven rejections between both groups | Type of biopsy-proven rejections between both groups at 12 months after transplantation | 12month | 
| Severity of biopsy-proven rejections between both groups | Severity of biopsy-proven rejections between both groups at 12 months after transplantation | 12month | 
| Outcome of biopsy-proven rejections between both groups | Outcome of biopsy-proven rejections between both groups at 12 months after transplantation | 12month | 
| Incidence of death | Incidence of death at 12 months after transplantation | 12 months | 
| Incidence of allograft loss | Incidence of allograft loss at 12 months after transplantation | 12 months | 
| Economic impact of implementing biomarkers in European Healthcare systems (cost/benefit) | Economic impact of implementing biomarkers in European Healthcare systems (cost/benefit) at 12 months after transplantation | up to 12 months | 
| Health-related Quality of life (QoL) of transplant patients after receiving a user-friendly reporting format from the EU-TRAIN report. | Health-related Quality of life (QoL) of transplant patients after receiving a user-friendly reporting format from the EU-TRAIN report. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal transplantation, non-invasive biomarkers, risk evaluation, randomized trial