LEOPARD Prospective Validation Cohort 1

NCT ID: NCT06723275

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

630 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-01-31

Study Completion Date

2027-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Decompensated Liver Cirrhosis Primary Biliary Cholangitis Primary Sclerosing Cholangitis Hepato-cellular Carcinoma

Keywords

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Liver transplantation Predictive models Liver transplantation candidates prospective longitudinal study

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Subset 1

Decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology

Standardized assessments and biobanking

Intervention Type OTHER

* 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

Subset 2

Other chronic end-stage liver diseases requiring LT, listed under MELD offering schemes, including notably but not exclusively cholestatic diseases, primary biliary cholangitis, primary sclerosing cholangitis

Standardized assessments and biobanking

Intervention Type OTHER

* 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

Subset 3

Hepato-cellular carcinoma as primary diagnosis, whatever the etiology of the underlying liver disease with or without underlying cirrhosis

Standardized assessments, guided tumor biopsy and biobanking

Intervention Type OTHER

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

Interventions

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Standardized 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

Intervention Type OTHER

Standardized 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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Luxembourg

OTHER

Sponsor Role collaborator

Hospital Universitario La Fe

OTHER

Sponsor Role collaborator

ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK (ECRIN)

UNKNOWN

Sponsor Role collaborator

Ophiomics - Precision Medicine

UNKNOWN

Sponsor Role collaborator

EF CLIF

UNKNOWN

Sponsor Role collaborator

INSERM 1149

UNKNOWN

Sponsor Role collaborator

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

OTHER_GOV

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent

Ghent, Belgium, Belgium

Site Status

Hospital Henri Mondor, Department of Hepatology

Créteil, France, France

Site Status

Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine

Kiel, Germany, Germany

Site Status

Italian National Transplant Center

Roma, Italy, Italy

Site Status

Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC)

Leiden, Netherlands, Netherlands

Site Status

Countries

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Belgium France Germany Italy Netherlands

Central Contacts

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Christophe DUVOUX, MD-PHD

Role: CONTACT

Phone: 01 49 81 23 25

Email: [email protected]

Nihel BERREBEH, Project Manager

Role: CONTACT

Phone: 01 40 27 46 20

Email: [email protected]

Facility Contacts

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Xavier Verhelst, MD-PHD

Role: primary

Christophe Duvoux, MD-PHD

Role: primary

Felix Braun, MD-PHD

Role: primary

Silvia Trapani, MD

Role: primary

Minneke Coenraad, MD-PHD

Role: primary

Other Identifiers

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2024-A00808-39

Identifier Type: OTHER

Identifier Source: secondary_id

APHP231778

Identifier Type: -

Identifier Source: org_study_id