LEOPARD Training and Validation Data Collection Study

Official title

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

Overview

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.

Primary outcome measures

• 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. [Time frame: 3 months after listing in subsets 1 & 2 ; 12 months after listing in subset3]

Secondary outcome measures (9)

• Number of participants with 6- and 9-month pre LT mortality dropout for being too sick (all subsets) [Time frame: 6 and 9 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]
• 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 to 12 months]
• Time from listing to death/dropout [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]
• Time to transplantation [Time frame: 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 [Time frame: 6 months and 12 months after liver transplantation]
• Number of participants with 12-month HCC recurrence in subset 3 [Time frame: 12 months after liver transplantation]
• Number of participants with 6-month post-LT survival (all subsets) [Time frame: 6 month after liver transplantation]
• 6-month transplant benefit (all subsets) [Time frame: 6 months after liver transplantation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 17 centers

• Università Politecnica delle Marche — Ancona
• Aou Policlinico di Bari — Bari
• Hepatobiliary Surgery and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bolo — Bologna
• Ospedale Policlinico San Martino — Genova
• Division of General Surgery & Abdominal Transplantation, Asst Grande Ospedale Metropolitan — Milan
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Azienda Ospedaliero Universita — Modena
• Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli — Naples
• … and 9 more centers

France · 16 centers

• CHU Jean Minjoz Besançon, Department of Hepatology — Besançon
• CHU Trousseau Tours, Department of Hepatology — Chambray-lès-Tours
• CHU Beaujon, Department of Hepatology — Clichy
• Hospital Henri Mondor, Department of Hepatology — Créteil
• CHU Dijon, Department of Hepatology — Dijon
• CHRU Huriez Lille, Department of Hepatology — Lille
• CHU Lyon Croix Rousse, Department of Hepatology — Lyon
• CHU La Timone AP-HM, Department of Hepatology — Marseille
• … and 8 more centers

Germany · 9 centers

• Department for General, Visceral, Pediatric and Transplant Surgery, Universitätsklinikum A — Aachen
• Charité - Universitätsmedizin Berlin — Berlin
• Gastroenterology, Hepatology, Infectious Diseases and Endocrinology (GHIE) Medizinische Ho — Hanover
• Universitätsklinikum Jena — Jena
• Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine — Kiel
• Universität Leipzig — Leipzig
• Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münst — Münster
• Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübin — Tübingen
• … and 1 more center

Belgium · 5 centers

• Hôpital Erasme Université Libre de Bruxelles — Brussels
• Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent — Ghent
• Cliniques Universitaires Saint-Luc (UCLouvain) — Leuven
• UZ Leuven — Leuven
• CHU Liège — Liège

Spain · 3 centers

• Department of General, Visceral and Transplantation Surgery, Hospital Universitario Virgen — Murcia
• Hospital Universitario Virgen del Rocío — Seville
• Hospital General Universitari València — Valencia

Netherlands · 2 centers

• Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC) — Leiden
• Gastroenterology and Hepatology, Rotterdam Erasmus Medical Center — Rotterdam

Austria · 1 center

• Universitätsklinik für Allgemeinchirurgie, Klinische Abteilung für Transplantation — Vienna

Identifiers

NCT: NCT06675604 · APHP240880

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗