Clinical trial NCT06761482: Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Official title: Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pediatric Kidney Disease
Transplant;Failure,Kidney
Keywords: kidney
transplant
pediatric
rejection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-01-07
Enrollment: 160
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open label multicenter prospective randomized trial of superiority with two active comparators / 4 groupes : monitoring by dd-cfDNA; monitoring by T-Vis; monitoring by dd-cfDNA+ T-Vis; Current standard of care based on surveillance biopsies and biological monitoring
Primary purpose: OTHER

Brief summary: Currently, the monitoring of children receiving a kidney transplantation includes surveillance biopsies to detect subclinical rejection and signs of toxicity of immunosuppressive drugs (tacrolimus).

The hypothesis of the study is that the combination of non-invasive biomarkers (Donor-derived cell-free DNA and Virus-specific T cells) will allow both the safe discontinuation of surveillance biopsies and the personalization of the exposure to calcineurin inhibitors among pediatric kidney transplant recipients.

Detailed description: MONITOR is an open label multicenter prospective randomized trial of superiority with two active comparators (4 parallel groups 1:1:1:1).

Arm A: monitoring by dd-cfDNA; Arm B: monitoring by T-Vis; Arm C: monitoring by dd-cfDNA+ T-Vis; Comparator arm: Current standard of care based on surveillance biopsies and biological monitoring

Main objectives and primary endpoints :

1. To demonstrate that the use of an integrative score of allograft rejection including dd-cfDNA measurement allows the reduction of the number of surveillance biopsies.

   Endpoint: Number of biopsy performed in each arm
2. To demonstrate that steering immunosuppression based on Tvis numbers allows the reduction of the exposition to calcineurin inhibitors.

Endpoint: Tacrolimus exposure assessed as the mean of the residual concentration of Tacrolimus between M6 and M24

Eligibility criteria: Inclusion Criteria:

* Age less than 21 years old at transplantation
* Single renal transplant from a deceased or a living donor.
* Absence of pregnancy confirmed by a negative pregnancy test in women in child-bearing period.
* Subject and legal guardians are willing and able to provide signed written informed consent and to comply with the study procedures
* Patients affiliated to health insurance system including Aide Médicale de l'Etat (AME)

Exclusion Criteria:

* History of multi-organ transplant (interference with rejection natural history)
* No surveillance biopsy planned
* Adult patient (or legal guardians) with limited understanding of the French language preventing him from receiving informed information on the protocol

Primary outcomes:
measure: Number of kidney allograft during the 2 years post-transplantation
timeFrame: 24 months
measure: Exposure to calcineurin inhibitors (mean tacrolimus level) between month 6 and month 24 post-transplantation.
timeFrame: 24 months
Secondary outcomes:
measure: Number of participants with adverse events as assessed by CTCAE v4.0 in each group
timeFrame: 24 months
measure: Cost-utility
timeFrame: 24 months
measure: Allograft fibrosis on the surveillance biopsy at 24 months
timeFrame: 24 months
measure: Allograft function (estimated Glomerular Filtration Rate) at 24 months
timeFrame: 24 months
measure: Predicted allograft survival until 10 years after evaluation
timeFrame: 10 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Robert Debré Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Julien HOGAN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: