Clinical trial NCT06406179: Evaluation of the Efficacy of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients"
Official title: Randomized Controlled Multicenter Trial to Evaluate the Efficacy and Safety of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Renal Transplantation
Keywords: renal transplantation rejection
non-invasive biomarker (dd-cfDNA )
risk evaluation
randomized trial
Gene expression
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-05-09
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 18-months follow-up national, multicenter, prospective , 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"): during the first 18 months after transplantation, patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria). Allograft biopsies will be performed according the clinical practice of the center and the medical decision during the visits at M3, M12 or for clinical indication (CI).
* Group II ("dd-cfDNA-guided"): As in the routine group at M3, M12 and at CI visits, patients will have clinical follow-up based on the investigators' routines. In addition, physicians will receive a report containing dd-cfDNA results and relevant medical parameters to help them decide whether or not to perform a biopsy.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: compare levels of eGFR measured by CKD-EPI equation in both arms
timeFrame: 18 months
Secondary outcomes:
measure: modification of the immunosuppression treatment
timeFrame: 18 months
measure: graft survival rates
timeFrame: 18 months
measure: biopsy-proven rejections
timeFrame: 18 months
measure: incidence of death
timeFrame: 18 months
measure: probability of kidney allograft rejection measured by gene expression in the biopsy tissue
timeFrame: 18 months
measure: quantity of lesion patterns between both groups
timeFrame: 18 months
measure: compare health care expenses between both groups
timeFrame: 18 months
measure: compare EQ-5D-5L questionnaire answers between both group
timeFrame: 18 months
measure: compare the PREMs questionnaire answer in dd-cfDNA-guided group
timeFrame: 18 months
measure: compare the GAD-7 questionnaire answer between both group
timeFrame: 18 months
measure: compare the VAS questionnaire answer between both group
timeFrame: 18 months
Other outcomes:
measure: rate of biopsies
timeFrame: 18 months
Locations:
city: Paris
country: France
facility: Hopital Saint Louis
state: Ile De France
city: Paris
country: France
facility: Hôpital de la Salpêtrière hôpital à Paris
state: Ile De France
city: Paris
country: France
facility: Georges Pompidou European Hospital
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Paris
country: France
facility: AP-HP - Hôpital Tenon
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: APHP
name: Alexandre Loupy, PR
role: STUDY_DIRECTOR
References: