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NCT Number: NCT06406179

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

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.

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Key information

Conditions

Renal Transplantation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hopital Saint Louis, Paris, Île-de-France Region, France

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

dd-cfDNA-guided

Biological

In groups I and II, the blood sample for dd-cfDNA assay will be taken on D0, just prior to transplantation, for all patients.

in addition, for patients following a dd-cf DNA-guided strategy based on dd-cf DNA ; samples for dd-cf DNA assay will be taken at M3 and M12 visits and at visits for clinical indication (5 maximum) and the blood will be sent to the PARCC technical platform of INSERM UMR 970. By combining the dd-cfDNA level and relevant medical data, an integration report will be sent to the centers to stratify patients into high-risk or low-risk rejection profiles.

If the patient is classified in the "low risk of rejection" subgroup, he may decide not to perform the biopsy. If the patient is classified in the "high risk of rejection" subgroup, he may decide to perform the biopsy within 15 days of the sample being taken. the decision to perform the biopsy is left to the discretion of the physician.

Primary outcomes

  1. compare levels of eGFR measured by CKD-EPI equation in both arms

    Time frame: 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 outcomes

  1. modification of the immunosuppression treatment

    Time frame: 18 months

    To assess the rate of modification of the immunosuppression treatment in both groups

  2. graft survival rates

    Time frame: 18 months

    To assess predicted graft survival rates in both groups using the iBox

  3. biopsy-proven rejections

    Time frame: 18 months

    compare the rate of biopsy-proven rejections in both groups

  4. incidence of death

    Time frame: 18 months

    compare the incidence of death and allograft loss in both groups

  5. probability of kidney allograft rejection measured by gene expression in the biopsy tissue

    Time frame: 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);

  6. quantity of lesion patterns between both groups

    Time frame: 18 months

    identify and compare lesion patterns imaging that are associated with response to rejection therapy using Digital Pathology (immunosuppression dose and response).

  7. compare health care expenses between both groups

    Time frame: 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.

  8. compare EQ-5D-5L questionnaire answers between both group

    Time frame: 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).

  9. compare the PREMs questionnaire answer in dd-cfDNA-guided group

    Time frame: 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)

  10. compare the Generalised Anxiety Disorder Assessment (GAD-7 ) questionnaire answer between both group

    Time frame: 18 months

    compare the evolution of patient's well-being during the first 18 months after kidney

  11. compare the visual analyse scale ( VAS ) questionnaire answer between both group

    Time frame: 18 months

    compare the evolution of patient's well-being during the first 18 months after kidney

Other outcomes

  1. rate of biopsies

    Time frame: 18 months

    Comparison of The mean eGFR in both Groups estimated by glomerular filtration rate (CKD-EPI eGFR) at 12 months' post-transplantation and of the number of allograft rejection.

Study contacts

Contact information is provided by the study sponsor or research team.

Lefaucheur, Carmen, PR

CONTACT

[email protected]

+33676604946

Racape Maud, PHD

CONTACT

[email protected]

+33 7 50 92 26 57

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

Randomized Controlled Multicenter Trial to Evaluate the Efficacy and Safety of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients

Acronym: AI-CARE

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
May 9, 2024
Registry last updated
Sep 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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