Quantify the Benefits of Biomarkers in Routine Patient Care in Kidney Transplant Recipients (EUTRAIN IMPACT)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Renal Transplantation
• Intervention / Treatment: Biological: biomarker-guided strategy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carmen Lefaucheur, Pr; Phone Number: +33676604946; Email: carmenlefaucheur4@gmail.com
• Study Contact Backup: Name: Elias Michelle; Phone Number: +330142494949; Email: michelle.elias@aphp.fr

Study Locations

• France
  • Nantes, France, 44000
    • Nantes Hospital
  • Ile De France
    • Paris, Ile De France, France, 75010
      • Saint-Louis Hospital, Paris
    • Paris, Ile De France, France, 75015
      • Necker Hospital, Paris
• Germany
  • Berlin, Germany, 10117
    • Charité-Universitätsmedizin, Berlin
  • Berlin, Germany, 10117
    • Charité-Universitätsmedizin,
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Hospital
  • Barcelona, Spain, 08907
    • Bellvitge University Hospital
• Switzerland
  • Geneve
    • Geneva, Geneve, Switzerland, 1205
      • Geneva University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All men and women, age ≥18 years old.
2. Subject must be a recipient of a single renal transplant from a deceased or living donor.
3. Subject is willing and able to provide signed written informed consent and willing to comply with study procedures
4. 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:

1. Subject with Hepatitis B chronic infection and/or active infection by Hepatitis C virus (positive blood PCR result at the moment of transplant).
2. Subjects with known human immunodeficiency virus (HIV) infection.
3. Patients with active systemic infection that requires the continued use of antibiotics.
4. Patients with neoplasia except localized skin cancer receiving appropriate treatment.
5. 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.
6. Subjects who are legally detained in an official institution.
7. Primary non-function or early graft loss due to mechanical/surgical complications.
8. Death within the first 6 months after transplantation.
9. 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
10. History of multi-organ transplant (interference with rejection natural history).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 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). Visits with biopsies for clinical indication are left to the appreciation of the investigator
Experimental: 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. Visits with biopsies for clinical indication are left to the appreciation of the investigator	Biological: biomarker-guided strategy; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoint	Comparison of The mean eGFR in both Groups estimated by glomerular filtration rate (CKD-EPI eGFR) at 12 months' post-transplantation and of the number of allograft rejection.	up to 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Alexandre Loupy, Pr, APHP

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Anticipated): May 15, 2024
• Study Completion (Anticipated): May 15, 2024

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: randomized trial; renal transplantation; non-invasive biomarkers; risk evaluation
• Other Study ID Numbers: APHP200984

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No