LEOPARD Training and Validation Data Collection Study

Not yet recruiting

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

• Registration Number: NCT06675604
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-21
• Study Start: 2024-11
• Study First Submitted QC: 2024-11-04
• Last Update Submitted: 2024-11-04
• Study First Posted: 2024-11-05
• Last Update Posted: 2024-11-05
• Primary Completion: 2027-12
• Study Completion: 2028-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 4500

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.)

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 months after listing in subsets 1 & 2 ; 12 months after listing in subset3	* 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

Secondary Outcome Measures

Name	Time	Method
Number of participants with 6- and 9-month pre LT mortality dropout for being too sick (all subsets)	6 and 9 months after listing	Mortality (all subsets)
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	Causes of death/drop-out (all subsets)
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	delisting for patient's decision or clinical improvement
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	Duration from listing to death/dropout (days)
Time to transplantation	From date of listing until date of transplantation, assessed up to 12 months	Duration from listing to transplantation (days)
Number of participants with 6-month and 12 month post LT survival in subsets 1 to 3	6 months and 12 months after liver transplantation	Survival in Training cohort subsets 1 to 3
Number of participants with 12-month HCC recurrence in subset 3	12 months after liver transplantation	HCC recurrence in Training cohort subset 3
Number of participants with 6-month post-LT survival (all subsets)	6 month after liver transplantation	Survival in Validation cohort all subsets
6-month transplant benefit (all subsets)	6 months after liver transplantation	Relevant comorbidities (diabetes, hypertension, stroke, coronary disease, cancers, alcohol and tobacco consumption) in Validation cohort all subsets

Trial Locations

Locations (7)

Universitätsklinik für Allgemeinchirurgie, Klinische Abteilung für Transplantation; 🇦🇹 Vienna, Austria

Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent; 🇧🇪 Ghent, Belgium

Hospital Henri Mondor, Department of Hepatology; 🇫🇷 Créteil, France

Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine; 🇩🇪 Kiel, Germany

Italian National Transplant Center; 🇮🇹 Rome, Italy

Center for Liver Tumors Leiden of the Leiden University Medical Center (LUMC); 🇳🇱 Leiden, Netherlands

Servicio de HepatologíaHospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain