Pediatric Kidney Disease, Transplant;Failure,Kidney
Conditions
Keywords
kidney, transplant, pediatric, rejection
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
Interventions
PROCEDUREmonitoring by dd-cfDNA
monitoring by dd-cfDNA
PROCEDUREmonitoring by T-Vis
monitoring by T-Vis
PROCEDUREmonitoring by dd-cfDNA+ T-Vis
monitoring by dd-cfDNA+ T-Vis
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of kidney allograft during the 2 years post-transplantation | 24 months | 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. |
| Exposure to calcineurin inhibitors (mean tacrolimus level) between month 6 and month 24 post-transplantation. | 24 months | To demonstrate that steering immunosuppression based on Tvis numbers allows the reduction of the exposition to calcineurin inhibitors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Allograft fibrosis on the surveillance biopsy at 24 months | 24 months | — |
| Number of participants with adverse events as assessed by CTCAE v4.0 in each group | 24 months | 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. |
| Predicted allograft survival until 10 years after evaluation | 10 years | — |
| Allograft function (estimated Glomerular Filtration Rate) at 24 months | 24 months | — |
| Cost-utility | 24 months | 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 |
Countries
France
Contacts
Primary ContactJulien HOGAN, MD, PhD
Outcome results
None listed