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NCT Number: NCT06723275

LEOPARD Prospective Validation Cohort 1

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.

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Key information

Conditions

Decompensated Liver Cirrhosis Bile Duct Diseases Biliary Tract Diseases Cholangitis Cholangitis, Sclerosing Cholestasis Cholestasis, Intrahepatic Digestive System Diseases Fibrosis Hepato-cellular Carcinoma Liver Cirrhosis Liver Cirrhosis, Biliary Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Primary Biliary Cholangitis Primary Sclerosing Cholangitis

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent, Ghent, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Standardized assessments, guided tumor biopsy and biobanking

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

Standardized assessments and biobanking

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

Primary outcomes

  1. 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

Secondary outcomes

  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. Time to transplantation

    Time frame: From date of listing until date of transplantation, assessed up to 12 months

    Duration from listing to transplantation (days)

  8. 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

  9. Number of participants with 9-month HCC recurrence in subset 3

    Time frame: 9 months after liver transplantation

    HCC recurrence in subset 3

  10. 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

  11. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Christophe DUVOUX, MD-PHD

CONTACT

[email protected]

01 49 81 23 25 ext. +33

Nihel BERREBEH, Project Manager

CONTACT

[email protected]

01 40 27 46 20 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK (ECRIN)
  • EF CLIF
  • Hospital Universitario La Fe
  • INSERM 1149
  • Institut National de la Santé Et de la Recherche Médicale, France
  • Ophiomics - Precision Medicine
  • University of Luxembourg

Registry information

Official study 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

Acronym: LEOPARD PVC1

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Dec 9, 2024
Registry last updated
Dec 13, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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