Renal TransplantationAI-CARENCT06406179
Evaluation of the Efficacy of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients"
A study testing dd-cfDNA-guided in people with Renal Transplantation, run by Assistance Publique - Hôpitaux de Paris at 6 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- dd-cfDNA-guided
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 529 participants
- Where
- 6 sitesFrance
- Study dates
- 31 May 2025to 30 Nov 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
Georges Pompidou European Hospital
Paris, 75015
Hôpital Necker-Enfants Malades
Paris, 75015
AP-HP - Hôpital Tenon
Paris
Hopital Saint Louis
Paris, Île-de-France Region, 75010
Hôpital de la Salpêtrière hôpital à Paris
Paris, Île-de-France Region, 75013
CHU Toulouse
Toulouse
About this study
Official title: Randomized Controlled Multicenter Trial to Evaluate the Efficacy and Safety 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.
Read the detailed description
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
- Conditions
- Renal Transplantation
- Being tested
- dd-cfDNA-guided
- Keywords
- renal transplantation rejection, non-invasive biomarker (dd-cfDNA ), risk evaluation, randomized trial, Gene expression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dd-cfDNA-guidedBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Group I : routine group | No intervention | patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and a surveillance allograft biopsy performed at 3 and 12 months after transplantation (M3 and M12) and for clinical indication whenever considered necessary by the clinician (CI), on the basis of 5 CI visits maximum expected per patient between D0 and M18. 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 . |
| Group II: dd-cfDNA-guided | Experimental | 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 (5 CI visits maximum expected per patient between D0 and M18 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.
If the patient is stratified into the "high-risk of rejection" subgroup, they can decide to perform the biopsy. In any case, the decision to perform the biopsy is left to the appreciation of the physician. They will report their awareness of the report's result to guide the act of biopsy in the eCRF.
like in Group I, the standard of care comprises two biopsy cores Receives: Biological: dd-cfDNA-guided |
What is being measured
The primary outcome is the main question the study is designed to answer.
compare levels of eGFR measured by CKD-EPI equation in both arms
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
Measured: 18 months
Secondary outcomes (11)
modification of the immunosuppression treatment
To assess the rate of modification of the immunosuppression treatment in both groups
Measured: 18 months
graft survival rates
To assess predicted graft survival rates in both groups using the iBox
Measured: 18 months
biopsy-proven rejections
compare the rate of biopsy-proven rejections in both groups
Measured: 18 months
incidence of death
compare the incidence of death and allograft loss in both groups
Measured: 18 months
probability of kidney allograft rejection measured by gene expression in the biopsy tissue
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);
Measured: 18 months
quantity of lesion patterns between both groups
identify and compare lesion patterns imaging that are associated with response to rejection therapy using Digital Pathology (immunosuppression dose and response).
Measured: 18 months
compare health care expenses between both groups
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.
Measured: 18 months
compare EQ-5D-5L questionnaire answers between both group
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).
Measured: 18 months
compare the PREMs questionnaire answer in dd-cfDNA-guided group
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)
Measured: 18 months
compare the Generalised Anxiety Disorder Assessment (GAD-7 ) questionnaire answer between both group
compare the evolution of patient's well-being during the first 18 months after kidney
Measured: 18 months
compare the visual analyse scale ( VAS ) questionnaire answer between both group
compare the evolution of patient's well-being during the first 18 months after kidney
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2024
- Study start31 May 2025
- Primary completion30 Nov 2028 (estimated)
- Study completion30 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a 18-months follow-up national, multicenter, prospective , randomized, biomarker strategy design trial, whereby kidney transplant patients will be randomized 1:1 at the time of transplantation in 2 study groups. * Group I ("routine group"): during the first 18 months after transplantation, patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria). Allograft biopsies will be performed according the clinical practice of the center and the medical decision during the visits at M3, M12 or for clinical indication (CI). * Group II ("dd-cfDNA-guided"): As in the routine group at M3, M12 and at CI visits, patients will have clinical follow-up based on the investigators' routines. In addition, physicians will receive a report containing dd-cfDNA results and relevant medical parameters to help them decide whether or not to perform a biopsy.
- Masking
- None (open label)
- Enrolment
- 529 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandre Loupy, PR, Study director, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06406179
- Sponsor's protocol ID
- APHP231641
- Acronym
- AI-CARE
- Status last verified
- Oct 2026
- First submitted
- 29 Apr 2024
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Multicenter Trial to Evaluate the Efficacy and Safety of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT06406179
- Acronym / sponsor ID
- AI-CARE / APHP231641
- Conditions
- Renal Transplantation
- Keywords
- renal transplantation rejection, non-invasive biomarker (dd-cfDNA ), risk evaluation, randomized trial, Gene expression
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 529 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 31 May 2025 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 30 Nov 2028 (estimated)
- First posted
- 9 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a 18-months follow-up national, multicenter, prospective , randomized, biomarker strategy design trial, whereby kidney transplant patients will be randomized 1:1 at the time of transplantation in 2 study groups. * Group I ("routine group"): during the first 18 months after transplantation, patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria). Allograft biopsies will be performed according the clinical practice of the center and the medical decision during the visits at M3, M12 or for clinical indication (CI). * Group II ("dd-cfDNA-guided"): As in the routine group at M3, M12 and at CI visits, patients will have clinical follow-up based on the investigators' routines. In addition, physicians will receive a report containing dd-cfDNA results and relevant medical parameters to help them decide whether or not to perform a biopsy.
| Arm | Type | Receives |
|---|---|---|
| Group I : routine group | No intervention | –patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and a surveillance allograft biopsy performed at 3 and 12 months after transplantation (M3 and M12) and for clinical indication whenever considered necessary by the clinician (CI), on the basis of 5 CI visits maximum expected per patient between D0 and M18. 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 . |
| Group II: dd-cfDNA-guided | Experimental | Biological: dd-cfDNA-guidedPatients 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 (5 CI visits maximum expected per patient between D0 and M18 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. If the patient is stratified into the "high-risk of rejection" subgroup, they can decide to perform the biopsy. In any case, the decision to perform the biopsy is left to the appreciation of the physician. They will report their awareness of the report's result to guide the act of biopsy in the eCRF. like in Group I, the standard of care comprises two biopsy cores |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dd-cfDNA-guidedIn 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. | Biological | Group II: dd-cfDNA-guided |
Primary outcome
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
11 secondary outcomes
modification of the immunosuppression treatment
Time frame: 18 months
graft survival rates
Time frame: 18 months
biopsy-proven rejections
Time frame: 18 months
incidence of death
Time frame: 18 months
probability of kidney allograft rejection measured by gene expression in the biopsy tissue
Time frame: 18 months
quantity of lesion patterns between both groups
Time frame: 18 months
compare health care expenses between both groups
Time frame: 18 months
compare EQ-5D-5L questionnaire answers between both group
Time frame: 18 months
compare the PREMs questionnaire answer in dd-cfDNA-guided group
Time frame: 18 months
compare the Generalised Anxiety Disorder Assessment (GAD-7 ) questionnaire answer between both group
Time frame: 18 months
compare the visual analyse scale ( VAS ) questionnaire answer between both group
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
Related trials for Renal Transplantation
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandre Loupy, PR study director
APHP
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing dd-cfDNA-guided in people with Renal Transplantation, run by Assistance Publique - Hôpitaux de Paris at 6 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
compare levels of eGFR measured by CKD-EPI equation in both arms (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.