Clinical trial NCT06675604: LEOPARD Training and Validation Data Collection Study
Official title: Data Collection to Design and Validate LEOPARD Predictive Models of Delisting in Liver Transplant Candidates
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Decompensated Liver Cirrhosis
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Hepato-cellular Carcinoma
Keywords: Liver transplantation
predictive models
data collection cohort
liver transplantation candidates
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: European Society for Organ Transplantation (ESOT)-European Liver and Intestine Transplant Association (ELITA)ELITA
name: University of Luxembourg
name: Italian National Transplant Centre (CNT)
name: La Fe University hospital Valencia (HULAFE)
First posted: 2024-11-05
Enrollment: 4500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.


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

Primary outcomes:
measure: 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.
timeFrame: 3 months after listing in subsets 1 & 2 ; 12 months after listing in subset3
Secondary outcomes:
measure: Number of participants with 6- and 9-month pre LT mortality dropout for being too sick (all subsets)
timeFrame: 6 and 9 months after listing
measure: Causes of death/drop-out for being too sick
timeFrame: 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
measure: Incidence of delisting for patient's decision or clinical improvement
timeFrame: From date of inclusion until date of delisting for patient's decision or clinical improvement, assessed up to 12 months
measure: Time from listing to death/dropout
timeFrame: 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
measure: Time to transplantation
timeFrame: From date of listing until date of transplantation, assessed up to 12 months
measure: Number of participants with 6-month and 12 month post LT survival in subsets 1 to 3
timeFrame: 6 months and 12 months after liver transplantation
measure: Number of participants with 12-month HCC recurrence in subset 3
timeFrame: 12 months after liver transplantation
measure: Number of participants with 6-month post-LT survival (all subsets)
timeFrame: 6 month after liver transplantation
measure: 6-month transplant benefit (all subsets)
timeFrame: 6 months after liver transplantation
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Universitätsklinik für Allgemeinchirurgie, Klinische Abteilung für Transplantation
city: Ghent
country: Belgium
facility: Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent
city: Besançon
country: France
facility: CHU Jean Minjoz Besançon, Department of Hepatology
city: Chambray-lès-Tours
country: France
facility: CHU Trousseau Tours, Department of Hepatology
city: Clichy
country: France
facility: CHU Beaujon, Department of Hepatology
city: Créteil
country: France
facility: Hospital Henri Mondor, Department of Hepatology
city: Dijon
country: France
facility: CHU Dijon, Department of Hepatology
city: Lille
country: France
facility: CHRU Huriez Lille, Department of Hepatology
city: Lyon
country: France
facility: CHU Lyon Croix Rousse, Department of Hepatology
city: Marseille
country: France
facility: CHU La Timone AP-HM, Department of Hepatology
city: Montpellier
country: France
facility: CHRU Montpellier Saint Eloi, Department of Hepatology
city: Nice
country: France
facility: CHU L'Archet Nice, Department of Hepatology
city: Paris
country: France
facility: CHU La Pitié Salpêtrière, Department of Hepatology
city: Pessac
country: France
facility: CHU Bordeaux Haut Levêque, Department of Hepatology
city: Rennes
country: France
facility: CHU Pontchaillou Rennes, Department of Hepatology
city: Strasbourg
country: France
facility: CHRU Strasbourg, Chirurgie Hepato-bilio-pancreatique et transplantation hepatique Department
city: Toulouse
country: France
facility: CHU Purpan Toulouse, Department of Hepatology
city: Villejuif
country: France
facility: CHU Paul Brousse, Department of Hepatology
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine
city: Rome
country: Italy
facility: Italian National Transplant Center
city: Leiden
country: Netherlands
facility: Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC)
city: Valencia
country: Spain
facility: Servicio de HepatologíaHospital Universitario y Politécnico La Fe
Study officials:
References: