LEOPARD Training and Validation Data Collection Study (LEOPARD TVDCS)

Data Collection to Design and Validate LEOPARD Predictive Models of Delisting in Liver Transplant Candidates

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 and countries. 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 TVDCS is therefore to collect a large set of data in liver transplantation candidates listed in Europe a) to design and b) to validate LEOPARD 2nd generation AI-based predictive models of mortality/dropout The primary objective is to develop new 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 Hepato-cellular carcinoma (HCC).

Method:

Longitudinal multicenter prospective health care data collection cohort study in 2 sets : Training/development set : Prospective health care data collection in 3,000 patients listed in 50 centres across 7 countries and Validation set: Prospective health care data collection in 1,500 subsequent patients listed in the same 50 centres.

Study Overview

• Status: Recruiting
• Conditions: Primary Sclerosing Cholangitis; Primary Biliary Cholangitis; Decompensated Liver Cirrhosis; Hepato-cellular Carcinoma

• Study Type: Observational
• Enrollment (Estimated): 4500

Contacts and Locations

• Study Contact: Name: Christophe Duvoux, MD-PHD; Phone Number: +33 01 49 81 23 25; Email: christophe.duvoux@aphp.fr
• Study Contact Backup: Name: Nihel BERREBEH, Project Manager; Phone Number: +33 01 40 27 46 20; Email: nihel.berrebeh@aphp.fr

Study Locations

• Austria
  • Vienna, Austria
    • Recruiting
    • Universitätsklinik für Allgemeinchirurgie, Klinische Abteilung für Transplantation
    • Contact: Gabriela Berlakovich, MD-PHD
• Belgium
  • Ghent, Belgium
    • Not yet recruiting
    • Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent
    • Contact: Xavier Verhelst, MD-PHD
• France
  • Besançon, France, 25000
    • Recruiting
    • CHU Jean Minjoz Besançon, Department of Hepatology
    • Contact: Delphine Weil Verhoeven, MD; Phone Number: +33 03 81 66 87 54; Email: dweil@chu-besancon.fr
  • Chambray-lès-Tours, France, 37170
    • Recruiting
    • CHU Trousseau Tours, Department of Hepatology
    • Contact: Laure Elkrief, MD; Phone Number: +33 02 47 47 59 37; Email: l.elkrief@chu-tours.fr
  • Clichy, France, 92110
    • Recruiting
    • CHU Beaujon, Department of Hepatology
    • Contact: Olivier Roux, MD; Phone Number: +33 01 40 87 55 22; Email: olivier.roux@aphp.fr
  • Créteil, France, 94010
    • Recruiting
    • Hospital Henri Mondor, Department of Hepatology
    • Contact: Christophe Duvoux, MD-PHD; Phone Number: +33 01 49 81 23 25; Email: christophe.duvoux@aphp.fr
  • Dijon, France, 21069
    • Recruiting
    • CHU Dijon, Department of Hepatology
    • Contact: Marianne Latournerie, MD; Phone Number: +33 03 80 29 37 50; Email: marianne.latournerie@chu-dijon.fr
  • Lille, France, 59000
    • Recruiting
    • CHRU Huriez Lille, Department of Hepatology
    • Contact: Sébastien Dharancy, MD-PHD; Phone Number: +33 03 20 44 55 97; Email: Sebastien.DHARANCY@chru-lille.fr
  • Lyon, France, 69004
    • Not yet recruiting
    • CHU Lyon Croix Rousse, Department of Hepatology
    • Contact: Teresa Antonini, MD; Phone Number: +33 04 26 73 28 88; Email: teresa.antonini@chu-lyon.fr
  • Marseille, France, 13005
    • Not yet recruiting
    • CHU La Timone AP-HM, Department of Hepatology
    • Contact: Clara Dassetto, MD; Phone Number: +33 04 91 38 00 00; Email: Clara.DASSETTO@ap-hm.fr
  • Montpellier, France, 34295
    • Recruiting
    • CHRU Montpellier Saint Eloi, Department of Hepatology
    • Contact: Jose Ursic-Bedoya, MD-PHD; Phone Number: +33 04 67 33 67 33; Email: jose.ursicbedoya@chu-montpellier.fr
  • Nice, France, 06000
    • Recruiting
    • CHU L'Archet Nice, Department of Hepatology
    • Contact: Rodolphe Anty, MD-PHD; Phone Number: +33 04.92.03.66.00; Email: anty.r@chu-nice.fr
  • Paris, France, 75013
    • Recruiting
    • CHU La Pitié Salpêtrière, Department of Hepatology
    • Contact: Alessandra Mazzola, MD; Phone Number: +33 01 42 17 56 88; Email: alessandra.mazzola2@aphp.fr
  • Pessac, France, 33604
    • Recruiting
    • CHU Bordeaux Haut Levêque, Department of Hepatology
    • Contact: Faiza Chermak, MD; Phone Number: +33 05 57 65 64 39 f; Email: faiza.chermak@chu-bordeaux.fr
  • Rennes, France, 35033
    • Recruiting
    • CHU Pontchaillou Rennes, Department of Hepatology
    • Contact: Baptiste Giguet, MD; Phone Number: +33 02 99 28 53 25; Email: Baptiste.GIGUET@chu-rennes.fr
  • Strasbourg, France, 67000
    • Recruiting
    • CHRU Strasbourg, Chirurgie Hepato-bilio-pancreatique et transplantation hepatique Department
    • Contact: Baptiste Michard, MD; Phone Number: +33 03 88 12 79 19; Email: baptiste.michard@chru-strasbourg.fr
  • Toulouse, France, 31059
    • Recruiting
    • CHU Purpan Toulouse, Department of Hepatology
    • Contact: Marie-Angèle Robic, MD; Phone Number: +33 05 61 32 34 14; Email: robic.ma@chu-toulouse.fr
  • Villejuif, France, 94800
    • Recruiting
    • CHU Paul Brousse, Department of Hepatology
    • Contact: Audrey Coilly, MD-PHD; Phone Number: +33 01 45 59 30 28; Email: audrey.coilly@aphp.fr
• Germany
  • Kiel, Germany
    • Recruiting
    • Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine
    • Contact: Felix Braun, MD-PHD
• Italy
  • Rome, Italy
    • Not yet recruiting
    • Italian National Transplant Center
    • Contact: Giuseppe Feltrin, MD
• Netherlands
  • Leiden, Netherlands
    • Not yet recruiting
    • Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC)
    • Contact: Minneke Coenraad, MD-PHD
• Spain
  • Valencia, Spain
    • Not yet recruiting
    • Servicio de HepatologíaHospital Universitario y Politécnico La Fe
    • Contact: Marina Berenguer, MD-PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults patients listed for :

• Decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology (subset 1)
• Other chronic end-stage liver diseases requiring LT, to be listed under a MELD-based allocation system (examples: primary biliary cholangitis, primary sclerosing cholangitis etc…) (subset 2)
• Hepato-cellular carcinoma as primary diagnosis, whatever the etiology of the underlying liver disease with or without underlying cirrhosis (subset 3)

Description

Inclusion Criteria:

• Adult [age 18;70] patients listed for:

  • decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology (subset 1) OR
  • other chronic end-stage liver diseases requiring LT, to be listed under a MELD-based allocation system (examples: primary biliary cholangitis, primary sclerosing cholangitis etc…) (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 and MELD exceptions are affected or not.
• Patient (or trusted person, family member or close relation, if the patient is unable to be informed) who has been informed and did not express opposition to data collection

(*Of note, enrolment of patients with T1 tumors (1 single tumor < 2 cm diameter) not amenable to loco-regional therapies because of decompensation, and prioritized under the MELD system, will be allowed in Subset 1.)

Exclusion Criteria:

• Tumor vascular invasion (portal or hepatic veins) evidenced by imaging at pre transplantation work-up, including portal vein thrombosis stage 1
• Extra-hepatic metastasis of HCC, as assessed by sectional imaging, functional imaging (18 FDG PET CT/MRI) or histologically proven
• Patients who are under safeguard of justice or tutorship or curatorship
• Patient on AME (state medical aid)
• Participation to LEOPARD PVC 1 study of WP2

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Subset 1; Decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology
Subset 2; Other chronic end-stage liver diseases requiring LT, to be listed under a MELD-based allocation system (examples: primary biliary cholangitis, primary sclerosing cholangitis etc…)
Subset 3; Hepato-cellular carcinoma as primary diagnosis, whatever the etiology of the underlying liver disease with or without underlying cirrhosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical primary endpoint considered as the event of interest to be predicted will be a composite of number of participants with mortality or drop out for being too sick on transplantation waiting list.	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 subset3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with 6- and 9-month pre LT mortality dropout for being too sick (all subsets)	Mortality (all subsets)	6 and 9 months after listing
Causes of death/drop-out for being too sick	Causes of death/drop-out (all subsets)	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	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 to 12 months
Time from listing to death/dropout	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
Time to transplantation	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 and 12 month post LT survival in subsets 1 to 3	Survival in Training cohort subsets 1 to 3	6 months and 12 months after liver transplantation
Number of participants with 12-month HCC recurrence in subset 3	HCC recurrence in Training cohort subset 3	12 months after liver transplantation
Number of participants with 6-month post-LT survival (all subsets)	Survival in Validation cohort all subsets	6 month after liver transplantation
6-month transplant benefit (all subsets)	Relevant comorbidities (diabetes, hypertension, stroke, coronary disease, cancers, alcohol and tobacco consumption) in Validation cohort all subsets	6 months after liver transplantation

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: University of Luxembourg; European Society for Organ Transplantation (ESOT)-European Liver and Intestine Transplant Association (ELITA)ELITA; Italian National Transplant Centre (CNT); La Fe University hospital Valencia (HULAFE)

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): February 4, 2029

Study Registration Dates

• First Submitted: October 21, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 9, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Liver transplantation; predictive models; data collection cohort; liver transplantation candidates
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Carcinoma, Hepatocellular; Cholangitis; Cholangitis, Sclerosing; Liver Cirrhosis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: APHP240880

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared. Datas are own by Assistance Publique-Hôpitaux de Paris (AP-HP), 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