LEOPARD Training and Validation Data Collection Study

NCT06675604 | Recruiting

• 1 other identifier: APHP240880
• Study Type: observational
• Target: 4,500
• Locations: 7 countries
• Sites: 22

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 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.

Conditions

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

Keywords

Liver transplantation; predictive models; data collection cohort; liver transplantation candidates

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Number of participants with 6- and 9-month pre LT mortality dropout for being too sick (all subsets)

  6 and 9 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 to 12 months

• Time from listing to death/dropout

  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

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

Study Arms (3)

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

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

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)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (22)

Universitätsklinik für Allgemeinchirurgie, Klinische Abteilung für Transplantation

Vienna, Austria

RECRUITING

Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent

Ghent, Belgium

NOT YET RECRUITING

CHU Jean Minjoz Besançon, Department of Hepatology

Besançon, 25000, France

RECRUITING

CHU Trousseau Tours, Department of Hepatology

Chambray-lès-Tours, 37170, France

RECRUITING

CHU Beaujon, Department of Hepatology

Clichy, 92110, France

RECRUITING

Hospital Henri Mondor, Department of Hepatology

Créteil, 94010, France

RECRUITING

CHU Dijon, Department of Hepatology

Dijon, 21069, France

RECRUITING

CHRU Huriez Lille, Department of Hepatology

Lille, 59000, France

RECRUITING

CHU Lyon Croix Rousse, Department of Hepatology

Lyon, 69004, France

NOT YET RECRUITING

CHU La Timone AP-HM, Department of Hepatology

Marseille, 13005, France

NOT YET RECRUITING

CHRU Montpellier Saint Eloi, Department of Hepatology

Montpellier, 34295, France

RECRUITING

CHU L'Archet Nice, Department of Hepatology

Nice, 06000, France

RECRUITING

CHU La Pitié Salpêtrière, Department of Hepatology

Paris, 75013, France

RECRUITING

CHU Bordeaux Haut Levêque, Department of Hepatology

Pessac, 33604, France

RECRUITING

CHU Pontchaillou Rennes, Department of Hepatology

Rennes, 35033, France

RECRUITING

CHRU Strasbourg, Chirurgie Hepato-bilio-pancreatique et transplantation hepatique Department

Strasbourg, 67000, France

RECRUITING

CHU Purpan Toulouse, Department of Hepatology

Toulouse, 31059, France

RECRUITING

CHU Paul Brousse, Department of Hepatology

Villejuif, 94800, France

RECRUITING

Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine

Kiel, Germany

RECRUITING

Italian National Transplant Center

Rome, Italy

NOT YET RECRUITING

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

Leiden, Netherlands

NOT YET RECRUITING

Servicio de HepatologíaHospital Universitario y Politécnico La Fe

Valencia, Spain

NOT YET RECRUITING

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: October 21, 2024
• First Posted: November 5, 2024
• Study Start: February 4, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): February 4, 2029
• Last Updated: May 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); FR (16); ES (1); DE (1); NL (1); BE (1); IT (1)