The EU-TRAIN project has made significant progress, particularly through the successful execution of its first clinical trial. This trial recruited 550 kidney transplant patients. Biological samples were systematically collected at several critical time points: on the day of transplantation, three months post-transplant, twelve months post-transplant, and during any necessary clinical visits until 2021. These samples were analyzed to discover various key factors of organ rejection (non-invasive biomarkers), including specific antibodies related to Human-Leukocyte-Antigens (HLA), immune responses from peripheral blood mononuclear cells, non-HLA antibodies, and messenger RNA expression in both blood and biopsy tissues. This comprehensive analysis resulted in the creation of the EU-TRAIN database.
The data analysis focused on identifying variability among patients and developing predictive models for transplant rejection. The initial risk stratification system, which used standard clinical parameters alongside non-invasive biomarkers studied in the first trial, found that these biomarkers did not significantly enhance rejection predictions compared to standard of care alone. Consequently, donor-derived cell-free DNA (dd-cfDNA) was integrated into the predictive algorithm as a new potential non-invasive biomarker for further testing in the subsequent randomized controlled trial, named "Impact." The Impact study utilised the EU-TRACER algorithm based on dd-cfDNA levels in the blood at three months post-transplant to guide biopsy decisions. Additionally, patient-reported quality of life outcomes were monitored through health utility indices at various time points.
A clinical decision support system known as EU-TRACER-hom-ics was developed. This innovative system comprises three essential components: a user-friendly interface for clinicians, a computational integrator for data processing, and a secure distributed database for data storage. It allows for seamless integration of multiple data sources without manual entry, ensuring efficient data flow and high security. The EU-TRACER website was also enhanced to facilitate data reporting for clinicians and patients.
The Project Management Team oversaw financial management, deliverables, and communication with the European Commission. Throughout the last reporting period, the team guided the periodic report, organized a review meeting in October 2024, and ensured adherence to all relevant regulatory requirements.
Moreover, the consortium actively promoted non-invasive diagnostic tools for transplant rejection, including a final workshop in June 2024, fostering collaboration with patient associations and industry stakeholders.
