Decompensated Liver Cirrhosis, Hepato-cellular Carcinoma, Primary Biliary Cholangitis, Primary Sclerosing Cholangitis
Conditions
Keywords
Liver transplantation, Predictive models, Liver transplantation candidates, prospective longitudinal study
Brief summary
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.
Interventions
OTHERStandardized assessments, guided tumor biopsy and biobanking
Standardized 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
OTHERStandardized assessments and biobanking
* 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
Sponsors
Assistance Publique - Hôpitaux de Paris
University of Luxembourg
Hospital Universitario La Fe
ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK (ECRIN)
Ophiomics - Precision Medicine
EF CLIF
INSERM 1149
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adult \[age 18;70\] patients listed for: * 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. * Patient (or trusted person, family member or close relation, if the patient is unable to express consent) who has been informed and signed the informed consent. * Patient affiliated with a health insurance scheme (beneficiary or entitled party).
Exclusion criteria
* 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 * Patient on AME (state medical aid) * Participation in another trial including other studies proposed as part of the European LEOPARD project (cohort associated to WP1 \& WP5 ("LEOPARD TVDCS") or being in the exclusion period following previous interventional research involving the human person, if applicable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 months after listing in subsets 1 & 2 ; 12 months after listing in subset 3 | * 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with 6-month mortality/dropout for being too sick (subsets 1 to 3) | 6 months after listing | 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 | 9 months after listing | Mortality/dropout for being too sick |
| Number of participants with 12-month mortality/dropout for too sick in subset 3 | 12 months after listing | Mortality/dropout for being too sick |
| Causes of death/drop-out for being too sick | From date of inclusion until date of death from any cause or date of drop-out for being too sick, whichever came first, assessed up to 12 months | Causes of death/drop-out |
| Incidence of delisting for patient's decision or clinical improvement | From date of inclusion until date of delisting for patient's decision or clinical improvement, assessed up to12 months | Delisting for patient's decision or clinical improvement |
| Time from listing to death/drop-out | From date of listing until date of death from any cause or date of drop-out for being too sick, whichever came first, assessed up to 12 months | Duration from listing to death/dropout (days) |
| Time to transplantation | From date of listing until date of transplantation, assessed up to 12 months | Duration from listing to transplantation (days) |
| Number of participants with 1-year post transplant survival in subsets 1-2 | 12 months after liver transplantation | Survival in subsets 1-2 |
| Number of participants with 9-month HCC recurrence in subset 3 | 9 months after liver transplantation | HCC recurrence in subset 3 |
| Number of participants with 9-month post transplant survival in subset 3 | 9 months after liver transplantation | Post transplant survival in subset 3 |
| 9-month and 12-month transplant benefit in subsets 3 and 1-2, respectively | 9 months and 12 months after liver transplantation | Relevant comorbidities |
Countries
Belgium, France, Germany, Italy, Netherlands
Contacts
CONTACTChristophe DUVOUX, MD-PHD
CONTACTNihel BERREBEH, Project Manager
Outcome results
None listed