Assesment the Efficacy of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients"

Not Applicable

Not yet recruiting

• Conditions: Renal Transplantation
• Interventions: Biological: dd-cfDNA-guided

• Registration Number: NCT06406179
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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, biopsies are guided by dd-cfDNA at the same timepoints

Detailed Description

The main objective of this study is to demonstrate the ability of dd-cfDNA levels in the blood combined with clinical data to decrease the number of allograft biopsies during the first 18 months after transplantation.

500 new transplanted patients in 5 Frenchclinical 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 vasive, with a potential risk of complications for the patients and costly to the healthcare system.

Study Timeline

• Study First Submitted: 2024-04-29
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-05
• Study First Posted: 2024-05-09
• Last Update Submitted: 2024-05-13
• Last Update Posted: 2024-05-14
• Study Start: 2024-06-01
• Primary Completion: 2027-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 500

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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group II: dd-cfDNA-guided	dd-cfDNA-guided	Patients will follow a dd-cfDNA-guided strategy based on dd-cfDNA levels in the blood associated with relevant clinical data on the basis of its detection and prediction capacities for rejection at M3, M12 and during visits for clinical indication (3 CI visits maximum expected per patient between D0 and M18 as experienced in the EU-TRAIN Impact clinical study to be analyzed in the context of the AI-CARE trial) to decide whether a biopsy is performed within the first 18 months of follow-up. Patients will be classified in "High risk" and "Low risk" depending on the dd-cfDNA integrative report generated by PARCC INSERM UMR 970 after centralization of dd-cfDNA results. like in Group I, the standard of care comprises two biopsy cores: one is dedicated to histology. The paraffin-embedded core dedicated to SOC histology will be used for gene expression profiling and digital pathology imaging after SOC procedures in group II "high-risk" patients.

Primary Outcome Measures

Name	Time	Method
compare levels of eGFR measured by CKD-EPI equation in both arms	18 months	Comparison of the levels of eGFR (mL/min/1.73m2) in both arms estimated by glomerular filtration rate (CKD-EPI eGFR) at 18 months' post-transplantation

Secondary Outcome Measures

Name	Time	Method
graft survival rates	18 months	To assess predicted graft survival rates in both groups using the iBox
probability of kidney allograft rejection measured by gene expression in the biopsy tissue	18 months	determine the probability of different types of rejection (ABMR, TCMR, IFTA and Banff lesions) in kidney transplant recipients' biopsies using gene expression (variance explanation modelling);
modification of the immunosuppression treatment	18 months	To assess the rate of modification of the immunosuppression treatment in both groups
biopsy-proven rejections	18 months	compare the rate of biopsy-proven rejections in both groups
incidence of death	18 months	compare the incidence of death and allograft loss in both groups
quantity of lesion patterns between both groups	18 months	identify and compare lesion patterns imaging that are associated with response to rejection therapy using Digital Pathology (immunosuppression dose and response).
compare health care expenses between both groups	18 months	compare the cost/benefit of implementing dd-cfDNA monitoring compared to follow-up with the biopsy using the French health insurance database, evaluated at 18 months after transplantation.
compare the PREMs questionnaire answer in dd-cfDNA-guided group	18 months	Level of patient's understanding of their care with non-invasive monitoring and level of satisfaction with it (categorical scale answers from 0 up to 5)
compare EQ-5D-5L questionnaire answers between both group	18 months	compare the evolution of patient's well-being during the first 18 months after kidney transplantation using the EQ-5D-5L descriptive system and visual analog scale (VAS).

Trial Locations

Locations (5)

Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France

CHU Toulouse; 🇫🇷 Toulouse, France

Georges Pompidou European Hospital; 🇫🇷 Paris, France

Hopital Saint Louis; 🇫🇷 Paris, Ile De France, France

AP-HP - Hôpital Tenon; 🇫🇷 Paris, France