LEOPARD Prospective Validation Cohort 1

NCT06723275 | Not Yet Recruiting

• 2 other identifiers: APHP2317782024-A00808-39
• Study Type: observational
• Target: 630
• Locations: 5 countries
• Sites: 5

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. 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. 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.

Conditions

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

Keywords

Liver transplantation; Predictive models; Liver transplantation candidates; prospective longitudinal study

Outcome Measures

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

  * 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 Outcomes (11)

• Number of participants with 6-month mortality/dropout 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

  9 months after listing

• Number of participants with 12-month mortality/dropout for too sick in subset 3

  12 months after listing

• 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

• 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

Study Arms (3)

Subset 1

Decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology

Other: Standardized assessments and biobanking

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

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

Interventions

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

Subset 3

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

Subset 1; Subset 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (5)

Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent

Ghent, Belgium, Belgium

Location

Hospital Henri Mondor, Department of Hepatology

Créteil, France, 94010, France

Location

Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine

Kiel, Germany, Germany

Location

Italian National Transplant Center

Roma, Italy, Italy

Location

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

Leiden, Netherlands, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

For patients of subsets 1 and 2 : * Blood - 3 Dry tubes and 2 EDTA 5mL * Blood - 2 EDTA, 1 Li heparin, 2 citrate 5mL * Blood - 1 Tempus 10mL biobanking for DNA, RNA * Urine 1 plastic tube 5mL * Urine 1 hemolysis tube 5 mL * Ascites fluid 1 Dry tube 5mL For patients of subset 3 : * Blood - 1 Streck 10mL * Blood - 1 EDTA 5mL

MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cholangitis

Central Study Contacts

Christophe DUVOUX, MD-PHD

CONTACT

01 49 81 23 25; christophe.duvoux@aphp.fr

Nihel BERREBEH, Project Manager

CONTACT

01 40 27 46 20; nihel.berrebeh@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: December 9, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (1); FR (1); BE (1); IT (1)