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

Renal Transplantation Clinical Trial

— AI-CARE  

Official title:

Randomized Controlled Multicenter Trial to Sassess the Efficacy of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients"

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06406179
• Other study ID #: APHP231641
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 1, 2027

Study information

• Verified date: May 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Lefaucheur, Carmen, PR
• Phone: +33676604946
• Email: carmenlefaucheur4[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Biological:
• dd-cfDNA-guided
patients will follow an dd-cfDNA-guided strategy based on dd-cfDNA for immune monitoring; blood will be sampled at D0 only for patients with previous kidney transplant, at the M3 and M12 visits and at the visits for clinical indication (3 maximum ) and the blood shipped to PARCC INSERM UMR 970 technical platform. Combining dd-cfDNA level and relevant medical data, an integrative report will be sent to the centers stratifying patients into high- versus low-risk profiles of rejection. Patients stratified into a high-risk profile of rejection according to the report will undergo an allograft biopsy in the following 15 days after sampling; patients stratified into a low-risk profile of rejection will not undergo the biopsy.

Locations

Country	Name	City	State
France	AP-HP - Hôpital Tenon	Paris
France	Georges Pompidou European Hospital	Paris
France	Hôpital Necker-Enfants Malades	Paris
France	Hopital Saint Louis	Paris	Ile De France
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	rate of biopsies	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.	18 months
Primary	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	18 months
Secondary	modification of the immunosuppression treatment	To assess the rate of modification of the immunosuppression treatment in both groups	18 months
Secondary	graft survival rates	To assess predicted graft survival rates in both groups using the iBox	18 months
Secondary	biopsy-proven rejections	compare the rate of biopsy-proven rejections in both groups	18 months
Secondary	incidence of death	compare the incidence of death and allograft loss in both groups	18 months
Secondary	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);	18 months
Secondary	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).	18 months
Secondary	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.	18 months
Secondary	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).	18 months
Secondary	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)	18 months