Intro:
The present clinical research protocol is part of the LEOPARD European project (Grant n° 101080964 Horizon Europe) which aims to design and validate new predictive models of mortality among liver transplantation (LT) candidates.
MELD based-liver graft allocation systems have become increasingly inaccurate over the last decade to predict mortality/dropout of liver transplantation (LT) candidates on the waitlist (WL). Wide disparities in mortality/dropout on the WL also exist across European countries, ranging from 5 to 30% according to transplantation indications. In this setting, the European Commission- Horizon Europe funded-LEOPARD project intends to design new, 2nd generation, AI-machine learning-based predictive models of delisting in LT candidates, to better serve on time patients with the highest risk of dropout on the WL and to improve equity of access to LT across Europe.
Hypothesis/Objective The scientific justification of the LEOPARD PVC1 is therefore
1. to build an external cohort of LT candidates to test and validate the LEOPARD models, therefore providing robust evidence for adoption of LEOPARD models by Organ Sharing Organizations (OSOs). 2. to collect granular data, bio- and tissues sampes and images to test last-generation OMICs predictors and radiomics, therefore opening the door to design of 3rd generation, precision medicine-based predictive models.
The primary objective of the LEOPARD longitudinal study is to test and validate AI-based 2nd generation LEOPARD predictive models of mortality/drop out on the waitlist in patients with decompensated cirrhosis, or other end-stage chronic liver diseases, and in patients listed for HCC.
Method Multicenter Prospective longitudinal study in up to 630 enrolments (in case of replacing participants after inclusion) to obtain 600 patients meeting selection criteria, in 30 hospitals in 5 European countries including France, Italy, The Netherlands, Belgium and Germany.
decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology (subset1) OR
other end-stage liver diseases requiring LT, listed under MELD offering schemes (subset 2), including notably but not exclusively cholestatic diseases, primary biliary cholangitis, primary sclerosing cholangitis (subset 2) OR
HCC as primary diagnosis, whatever the etiology of the underlying liver disease with or without underlying cirrhosis (subset 3). (HCC diagnosed on Barcelona/EASL criteria or histologically proven. HCC meeting or not Milan criteria, as per center practice.)
Patients registered on national waiting lists under the MELD offering schemes, regardless of extra MELD points are affected or not.
Tumor vascular invasion (portal or hepatic veins) evidenced by imaging on pre transplantation work-up, including PVT stage 1
Extra-hepatic metastasis of HCC, as assessed by sectional imaging, functional imaging (18 FDG PET CT/MRI) or histologically proven
Women who are pregnant or nursing
Patients who are under safeguard of justice or tutorship or curatorship
Adult patients consecutively listed for LT for end-stage chronic liver diseases and HCC
Cohort
Prospective
Standardized assessments, guided tumor biopsy and biobanking
Other interventionStandardized assessment of Scores * Guided tumor biopsy in patients listed for hepatocellular carcinoma with active tumor at listing in centers not perfoming tumor biopsy on a routine basis * Additional blood sampling for biobanking and subsequent analysis of innovative biomarkers and OMICs * Urine sampling for biobanking and subsequent analysis of innovative biomarkers * Ascite sampling for biobanking and subsequent analysis * Tumor sampling for biobanking and subsequent analysis * Centralized assay for routine biomarkers
Standardized assessments and biobanking
Other intervention* Standardized assessment of Scores * Additional blood sampling for biobanking and subsequent analysis of innovative biomarkers and OMICs * Urine sampling for biobanking and subsequent analysis of innovative biomarkers * Ascite sampling for biobanking and subsequent analysis * Tumor sampling for biobanking and subsequent analysis * Centralized assay for routine biomarkers
Clinical primary endpoint will be a composite of mortality or drop out for being too sick on transplantation waiting list, since kinetics of dropout differs according to LT indications
* 3-month mortality/dropout for being too sick after listing in subsets 1 and 2 * 12-month mortality/dropout for being too sick (tumor progression) after listing in subset 3
Number of participants with 6-month mortality/dropout for being too sick (subsets 1 to 3)
Mortality/Drop out for being too sick (subsets 1 to 3)
Number of participants with 9-month mortality/dropout for too sick in subsets 1, 2
Mortality/dropout for being too sick
Number of participants with 12-month mortality/dropout for too sick in subset 3
Mortality/dropout for being too sick
Causes of death/drop-out for being too sick
Causes of death/drop-out
Click on the lead sponsor to view all of their trials.
Assistance Publique - Hôpitaux de Paris
Lead sponsor
University of Luxembourg
Collaborator
Hospital Universitario La Fe
Collaborator
ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK (ECRIN)
Collaborator
Ophiomics - Precision Medicine
Collaborator
EF CLIF
Collaborator
INSERM 1149
Collaborator
Institut National de la Santé Et de la Recherche Médicale, France
Collaborator
