Clinical trial NCT06723275: LEOPARD Prospective Validation Cohort 1
Official title: Validation of LEOPARD Predictive Models of Delisting in Liver Transplant Candidates: the LEOPARD Longitudinal Multicentre Prospective Validation Cohort 1, with Bio- and Tissue Collection
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Decompensated Liver Cirrhosis
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Hepato-cellular Carcinoma
Keywords: Liver transplantation
Predictive models
Liver transplantation candidates
prospective longitudinal study
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: University of Luxembourg
name: Hospital Universitario La Fe
name: ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK (ECRIN)
name: Ophiomics - Precision Medicine
name: EF CLIF
name: INSERM 1149
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2024-12-09
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients consecutively listed for LT for end-stage chronic liver diseases and HCC

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 3 months after listing in subsets 1 & 2 ; 12 months after listing in subset 3
Secondary outcomes:
measure: Number of participants with 6-month mortality/dropout for being too sick (subsets 1 to 3)
timeFrame: 6 months after listing
measure: Number of participants with 9-month mortality/dropout for too sick in subsets 1, 2
timeFrame: 9 months after listing
measure: Number of participants with 12-month mortality/dropout for too sick in subset 3
timeFrame: 12 months after listing
measure: Causes of death/drop-out for being too sick
timeFrame: 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
measure: Incidence of delisting for patient's decision or clinical improvement
timeFrame: From date of inclusion until date of delisting for patient's decision or clinical improvement, assessed up to12 months
measure: Time from listing to death/drop-out
timeFrame: 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
measure: Time to transplantation
timeFrame: From date of listing until date of transplantation, assessed up to 12 months
measure: Number of participants with 1-year post transplant survival in subsets 1-2
timeFrame: 12 months after liver transplantation
measure: Number of participants with 9-month HCC recurrence in subset 3
timeFrame: 9 months after liver transplantation
measure: Number of participants with 9-month post transplant survival in subset 3
timeFrame: 9 months after liver transplantation
measure: 9-month and 12-month transplant benefit in subsets 3 and 1-2, respectively
timeFrame: 9 months and 12 months after liver transplantation
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent
city: Créteil
country: France
facility: Hospital Henri Mondor, Department of Hepatology
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine
city: Roma
country: Italy
facility: Italian National Transplant Center
city: Leiden
country: Netherlands
facility: Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC)
Study officials:
References: