Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study (MONITOR)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pediatric Kidney Disease; Transplant;Failure,Kidney
• Intervention / Treatment: Procedure: monitoring by dd-cfDNA; Procedure: monitoring by T-Vis; Procedure: monitoring by dd-cfDNA+ T-Vis

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

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julien HOGAN, MD, PhD; Phone Number: +331 40 03 21 42; Email: julien.hogan@aphp.fr

Study Locations

• France
  • Paris, France, 75019
    • Robert Debré Hospital
    • Contact: Julien HOGAN, MD, PhD; Phone Number: +331 40 03 21 42; Email: julein.hogan@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: monitoring by dd-cfDNA	Procedure: monitoring by dd-cfDNA; monitoring by dd-cfDNA
Experimental: monitoring by T-Vis	Procedure: monitoring by T-Vis; monitoring by T-Vis
Experimental: monitoring by dd-cfDNA and T-Vis	Procedure: monitoring by dd-cfDNA+ T-Vis; monitoring by dd-cfDNA+ T-Vis
No Intervention: Current standard of care based on surveillance biopsies and biological monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of kidney allograft during the 2 years post-transplantation	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.	24 months
Exposure to calcineurin inhibitors (mean tacrolimus level) between month 6 and month 24 post-transplantation.	To demonstrate that steering immunosuppression based on Tvis numbers allows the reduction of the exposition to calcineurin inhibitors.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as assessed by CTCAE v4.0 in each group	Adverse events of particular interest will include de novo donor specific antibodies (DSA) formation, clinical rejection, plasma viral replication Cytomegalovirus Virus, Epstein-Barr virus, BK virus.	24 months
Cost-utility	Data sources for the latter will include the trial's case report form data for efficacy and resource consumption in terms of ambulatory care, informal care, and productivity losses. It will be complemented by participating hospitals' discharge data to gather information relative to hospital care and its associated costs. The effectiveness criteria will be the number of quality-adjusted life-years (QALYs) gained. QALYs will be derived from patients' responses to the EQ-5D questionnaire	24 months
Allograft fibrosis on the surveillance biopsy at 24 months		24 months
Allograft function (estimated Glomerular Filtration Rate) at 24 months		24 months
Predicted allograft survival until 10 years after evaluation		10 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Julien HOGAN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 30, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: transplant; pediatric; rejection; kidney
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Kidney Diseases
• Other Study ID Numbers: APHP230817; IDRCB 2024-A01418-39 (Registry Identifier: ANSM)

Drug and device information, study documents

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