Clinical trial NCT03582436: Rejection Diagnosis in Kidney Transplants Patients
Official title: Prospective KTD-innov Cohort of Kidney Transplants Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Transplant Rejection
Graft Survival
Keywords: Kidney
Allogeneic transplantation
Cohort study
Rejection
Biomarkers
Integrative medicine
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-07-11
Enrollment: 824
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: New kidney transplants patients

Brief summary: Main objective: To constitute a prospective multicentre French cohort of kidney transplant recipients including clinical, biological and immunological evaluation combined with non-invasive biomarkers in peripheral blood and urine, and gene expression assessment in allograft biopsy in order to increase the performance of rejection diagnosis in kidney transplant patients.

the investigators hypothesise that the addition of non-invasive biomarkers and intragraft assessment of gene expression profiles will improve the diagnosis capacity of histology in kidney transplant recipients as it reveals pathophysiological pathways that are not captured by light microscopy.

Detailed description: Rejection currently represents the major cause of allograft failure worldwide, with immediate consequences for the patients in terms of mortality, morbidity and costs for the society. The field of transplantation lacks robust assessments for immune monitoring and diagnoses. Currently, light microscopy still represents the gold standard, which has clearly been identified as imperfect. Given those facts, success of clinical trials is impaired with space for improvement of current diagnosis standards that should eventually lead to improved outcomes for kidney transplant recipients.

This study will provide the investigators with prospective data of kidney transplant patient that will allow the improvement of rejection diagnosis and individual immune monitoring for precision medicine: improvement of rejection diagnosis, stage and assessment of response to therapy. In order to estimate for each patient a probability of rejection, The investigators will generate algorithms using traditional clinical, biological and histological data that will be enriched by tissue as well as blood and urine non-invasive immune biomarkers.

These algorithms will be encapsulated in a "user-friendly" web-based application with best in-class visualisation : the TransplanScreen will display individual information with comparative and predictive context for clinicians and patients and better interfacing and communication. It will include a comprehensive TransplanScreen report based on the algorithms and included in Electronic Medical Record databases (object-oriented). It aims to provide visual and contextual information to promote personalised decision making, addressing the demand of public health authorities for improving efficiency and quality of care.

The expected benefit for participants and society will be to reduce the financial burden of graft rejection for society.

The cohort will include n=750 kidney transplant recipients in 8 French centres : 3 Parisian ones: Necker hospital, Saint-Louis Hospital and Bichat hospital and 4 regional ones: CHU Nantes, Toulouse and Bordeaux, Montpellier and Lyon Hospitals. Bichat hospital will not be recruiting but will contribute to the research.

Vulnerable participants excluded.

Schedule for the study:

* inclusion period: 12 months
* participation period (treatment - follow-up): 12 months
* total duration of the study: 24 months

Exclusion period for participation in other studies, and justification: the participation to other minimal risks and constraints studies and observational non-interventional studies is allowed during this study. There is no exclusion period at the end of study. The participation to other interventional and observational non-interventional studies is allowed after the end of the study.

Number of enrolments expected per site and per month :

* Necker Hospital: 14 patients / month
* Saint-Louis Hospital: 8 patients / month
* CHU Nantes: 10 patients / month
* Lyon Hospitals: 9 patients / month
* CHU Toulouse: 13 patients / month
* CHU Bordeaux: 9 patients / month.
* CHU Montpelier: 8/month

Eligibility criteria: Inclusion Criteria:

Men or female patients, Age ≥ 18 years old at the time of transplantation. Patients receiving a kidney transplant from a living or deceased donor. Patients who signed the informed consent form and willing to comply with study procedures.

Female patients of child-bearing potential must have a negative pregnancy test (serum beta-hCG) and must be practicing an effective, reliable and medically approved contraceptive regimen

Patients with a minimum weight of 40 kg

Exclusion Criteria:

History of multi-organ transplant (interference with rejection natural history).

Unable/unwilling to comply with study procedures (including foreign language speakers who are not assisted by a native French speaker).

Vulnerable participants (minors, protected adults, pregnant women, legally detained

Primary outcomes:
measure: Concordance of invasive/non-invasive biomarkers with allograft rejection
timeFrame: month 12
Secondary outcomes:
measure: Association of non-invasive biomarkers with different subtypes of rejection
timeFrame: month 12
measure: Association of gene sets with different subtypes of rejection in the biopsy.
timeFrame: month 12
measure: Reclassification capacity of gene sets and non-invasive biomarkers to define allograft rejection.
timeFrame: month 12
measure: Variation of the non-invasive biomarker signature of allograft rejection
timeFrame: month 12
measure: Variation of the gene set signature
timeFrame: month 12
measure: Cumulative incidence of antibody-mediated rejection (ABMR)
timeFrame: month 12
measure: Cumulative incidence of T-cell-mediated rejection (TCMR)
timeFrame: month 12
measure: Treatment failure rate
timeFrame: month 12
measure: Graft and patient survival
timeFrame: month 12
measure: Histological evidence of ABMR and/or TCMR on protocol biopsies
timeFrame: month 12
measure: Overall pathological changes, including chronic ABMR
timeFrame: month 12
measure: Incidence of delayed graft function
timeFrame: month 12
measure: Cumulative incidence and duration of dialysis.
timeFrame: month 12
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Saint-Louis
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Alexandre Loupy, Pr
role: STUDY_DIRECTOR
References: