Precision Risk Stratification in Kidney Transplant Patients - EU-TRAIN

NCT ID: NCT03652402

Last Updated: 2024-06-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 558 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-11-27
• Study Completion Date: 2021-10-28

Brief Summary

Main objective: To design a precision risk stratification system that predicts individual risk of rejection

Detailed Description

Allograft rejection is still a major threat to allografts with thousands of allografts failing every year worldwide due to organ rejection, with immediate consequences for the patients in terms of mortality and morbidity. With a prevalence around 20% in the first-year post transplant, rejection also carries high economic impact representing a 72% increase in transplantation price and downstream cost because of return on dialysis (60,000€ health care increase per patient). The rough estimates from 200,000 kidney allograft failures per year equals to 12 billion extra cost for the health care system per year.

Various explanations may be involved: 1) The current stratification system relies on various elements of the follow up of standard of care after kidney transplantation (histology, immunology) taken separately and, 2) Current therapeutic strategy is a "one fit for all" approach. Literature data show that therapeutics are not individualized, with 98% of patients having the same immunosuppressive regimens without analysis of response to therapy; 3) Lack of integration of omics in the stratification process. Today, the only approaches used to monitor the advent of immune-mediated allograft damage are nonspecific markers such as serum creatinine level and proteinuria which are not integrated in a dynamic approach. Some kidney transplant programs have implemented surveillance allograft biopsies, but they lack specificity and sensitivity and do not provide etiopathology of the underlying process. This impairs the risk stratification process.

In this project, leading European scientific teams, which have created relevant population cohorts and expertise, have joined forces to allow for large-scale (>5,000 patients) risk prediction studies in the field of kidney transplantation. The overall goal of the EUropean TRAnsplantation and INnovation consortium (EU-TRAIN) is to prevent kidney allograft failure and improve allograft survival by informing clinical decision and delivering optimised interventions to patients at individual level. The project aims to improve the current gold standard for risk stratification and prognosis among kidney transplant recipients.

The members of the EU-TRAIN consortium have invested heavily in the last decade to create large highly detailed European kidney transplant cohorts and to achieve best level scientific expertise in the assessment of innovative biomarkers and rejection reclassification on the basis of disease mechanism using gene expression. Ground-breaking concrete results have already been obtained that have changed patient care and transplant medicine guidelines: This is underlined by highly cited publications in the leading specialised journals and also in journals aimed at a popular audience that underlines the systemic nature of this approach, (NEJM (n=10), Lancet (n=2), BMJ (n=1), JASN (n=18)). Using this approach, the investigators have recently identified new forms of allograft rejection, resulting in changes in the most recent international allograft Banff classification and reclassifying rejection diagnosis and disease stage. This research strategy also led to recently demonstrate the clinical relevance of new non-invasive biomarkers for defining the pathogenicity of anti-HLA antibodies and allograft loss risk assessment and incorporate gene expression measurements in allograft rejection risk stratification.

The EU-TRAIN project will further elevate these cohorts synergistically by adding data on novel biomarkers, so far underdeveloped in kidney transplant research, in particular genomics and immunological data. A comprehensive integration strategy of these exceptionally large and complete cohorts constitutes a quantum leap in transplant research, and offers a unique opportunity, out of reach so far, to design strategies for truly personalised medicine.

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

500 new transplanted patients in the 7 clinical transplant sites will be included in the prospective multicentre EU-TRAIN cohort with centralised analysis of samples in CHUN (blood mRNA), ICS (blood cellular assays), Charité (non-HLA antibodies and blood endothelial targets), AP-HP (blood anti-HLA DSA), and INSERM (Biopsy mRNA).

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, Paris: 10 patients / month
• Saint-Louis Hospital, Paris: 6 patients / month
• CHU Nantes: 10 patients / month
• Charité-Universitätsmedizin, Campus Virchow Klinikum, Berlin: 4 patients / month
• Charité-Universitätsmedizin, Campus Mitte, Berlin: 3 patients / month
• Bellvitge University Hospital, Barcelona: 7 patients / month
• Geneva University Hospitals, Geneva: 2 patients / month
• Vall d'Hebron Hospital, Barcelona : 6 patients / month
• Kremlin Bicêtre Hospital, Paris : 4 patients / month

Conditions

Kidney Transplant Rejection; Kidney Transplantation; Risk Stratification; Prognosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

kidney transplantation

samples additional to the standard of care' (SOC)will be taken at each visit (Day 0, Month 3, Month12, clinical indication)

Intervention Type: PROCEDURE

Other Intervention Names

Gene expression analysis in the biopsy; Non-HLA antibody analysis in the blood; Protein biomarker analysis in the blood; T and B cell analyses in the blood; mRNA in the blood

Eligibility Criteria

Inclusion Criteria

• Men and women, Age ≥ 18 years old at the time of transplantation.
• Patients receiving a living or deceased donor kidney allograft.
• 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

Exclusion Criteria

• History of multi-organ transplant (interference with rejection natural history).
• Participant is unable or unwilling to comply with study procedures (including foreign language speakers who are not assisted by a native language speaker).
• Vulnerable participants (minors, protected adults, legally detained)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandre Loupy, Pr

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

Hôpital du Kremlin Bicêtre

Le Kremlin-Bicêtre, Paris, France

CHU Nantes

Nantes, , France

Hôpital Necker

Paris, , France

Hopital Saint Louis

Paris, Île-de-France Region, France

Hospital La Charité

Mitte, State of Berlin, Germany

Hospital La Charité Campus Virchow

Berlin, , Germany

Hospital Bellvitge

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hôpitaux Universitaires de Genève

Geneva, , Switzerland

Countries

France; Germany; Spain; Switzerland

References

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Related Links

http://link.springer.com/chapter/10.1007/978-3-030-75100-5_44#citeas

Secure Distribution of Factor Analysis of Mixed Data (FAMD) and Its Application to Personalized Medicine of Transplanted Patients

http://laas.hal.science/INRIA/hal-03747555v1

Distributing human leukocyte antigen HLA database in histocompatibility: a shift in HLA data governance

Other Identifiers

IDRCB 2018-A00733-52

Identifier Type: OTHER

Identifier Source: secondary_id

K170203J

Identifier Type: -

Identifier Source: org_study_id