LEOPARD Prospective Validation Cohort 1 (LEOPARD PVC1)

July 27, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Validation of LEOPARD Predictive Models of Delisting in Liver Transplant Candidates: the LEOPARD Longitudinal Multicentre Prospective Validation Cohort 1, With Bio- and Tissue Collection

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
630

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Belgium
    • Belgium
      • Ghent, Belgium, Belgium
        • Not yet recruiting
        • Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent
        • Contact:
          • Xavier Verhelst, MD-PHD
  • France
    • France
      • Clichy, France, France, 92110
        • Recruiting
        • Beaujon Hospital, Department of Hepatology
        • Contact:
      • Créteil, France, France, 94010
        • Recruiting
        • Hospital Henri Mondor, Department of Hepatology
        • Contact:
      • Montpellier, France, France, 34295
      • Paris, France, France, 75013
        • Recruiting
        • Hospital La Pitié Salpêtrière, Department of Hepato-gastro-enterology
        • Contact:
  • Germany
    • Germany
      • Kiel, Germany, Germany
        • Not yet recruiting
        • Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine
        • Contact:
          • Felix Braun, MD-PHD
  • Italy
    • Italy
      • Roma, Italy, Italy
        • Not yet recruiting
        • Italian National Transplant Center
        • Contact:
          • Silvia Trapani, MD
  • Netherlands
    • Netherlands
      • Leiden, Netherlands, Netherlands
        • Not yet recruiting
        • Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC)
        • Contact:
          • Minneke Coenraad, MD-PHD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients consecutively listed for LT for end-stage chronic liver diseases and HCC

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Subset 1
Decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology
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
Subset 3
Hepato-cellular carcinoma as primary diagnosis, whatever the etiology of the underlying liver disease with or without underlying cirrhosis
Other: 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
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
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
3 months after listing in subsets 1 & 2 ; 12 months after listing in subset 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to transplantation
Time Frame: From date of listing until date of transplantation, assessed up to 12 months
Duration from listing to transplantation (days)
From date of listing until date of transplantation, assessed up to 12 months
Number of participants with 6-month mortality/dropout for being too sick (subsets 1 to 3)
Time Frame: 6 months after listing
Mortality/Drop out for being too sick (subsets 1 to 3)
6 months after listing
Number of participants with 9-month mortality/dropout for too sick in subsets 1, 2
Time Frame: 9 months after listing
Mortality/dropout for being too sick
9 months after listing
Number of participants with 12-month mortality/dropout for too sick in subset 3
Time Frame: 12 months after listing
Mortality/dropout for being too sick
12 months after listing
Causes of death/drop-out for being too sick
Time Frame: 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
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
Incidence of delisting for patient's decision or clinical improvement
Time Frame: 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
From date of inclusion until date of delisting for patient's decision or clinical improvement, assessed up to12 months
Time from listing to death/drop-out
Time Frame: 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)
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
Number of participants with 1-year post transplant survival in subsets 1-2
Time Frame: 12 months after liver transplantation
Survival in subsets 1-2
12 months after liver transplantation
Number of participants with 9-month HCC recurrence in subset 3
Time Frame: 9 months after liver transplantation
HCC recurrence in subset 3
9 months after liver transplantation
Number of participants with 9-month post transplant survival in subset 3
Time Frame: 9 months after liver transplantation
Post transplant survival in subset 3
9 months after liver transplantation
9-month and 12-month transplant benefit in subsets 3 and 1-2, respectively
Time Frame: 9 months and 12 months after liver transplantation
Relevant comorbidities
9 months and 12 months after liver transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institut National de la Santé Et de la Recherche Médicale, France
Hospital Universitario La Fe
University of Luxembourg
Ophiomics - Precision Medicine
ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK (ECRIN)
EF CLIF
INSERM 1149

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 7, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 7, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 7, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 4, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP231778
  • 2024-A00808-39 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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