LEOPARD Prospective Validation Cohort 1 (LEOPARD PVC1)

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

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

Treatments: Other: Standardized assessments and biobanking; Other: Standardized assessments, guided tumor biopsy and biobanking

Study type: Observational

Funder types: Other

Identifiers

NCT06723275

APHP231778

2024-A00808-39 (Other Identifier)

Details and patient eligibility

About

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. 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 PVC1 is therefore

1. to build an external cohort of LT candidates to test and validate the LEOPARD models, therefore providing robust evidence for adoption of LEOPARD models by Organ Sharing Organizations (OSOs).
2. to collect granular data, bio- and tissues sampes and images to test last-generation OMICs predictors and radiomics, therefore opening the door to design of 3rd generation, precision medicine-based predictive models.

The primary objective of the LEOPARD longitudinal study is to test and validate AI-based 2nd generation LEOPARD 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 HCC.

Method Multicenter Prospective longitudinal study in up to 630 enrolments (in case of replacing participants after inclusion) to obtain 600 patients meeting selection criteria, in 30 hospitals in 5 European countries including France, Italy, The Netherlands, Belgium and Germany.

Enrollment: 630 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

  • decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology (subset1) OR
  • other end-stage liver diseases requiring LT, listed under MELD offering schemes (subset 2), including notably but not exclusively cholestatic diseases, primary biliary cholangitis, primary sclerosing cholangitis (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 are affected or not.

• Patient (or trusted person, family member or close relation, if the patient is unable to express consent) who has been informed and signed the informed consent.

• Patient affiliated with a health insurance scheme (beneficiary or entitled party).

Exclusion criteria

• Tumor vascular invasion (portal or hepatic veins) evidenced by imaging on pre transplantation work-up, including PVT stage 1
• Extra-hepatic metastasis of HCC, as assessed by sectional imaging, functional imaging (18 FDG PET CT/MRI) or histologically proven
• Women who are pregnant or nursing
• Patients who are under safeguard of justice or tutorship or curatorship
• Patient on AME (state medical aid)
• Participation in another trial including other studies proposed as part of the European LEOPARD project (cohort associated to WP1 & WP5 ("LEOPARD TVDCS") or being in the exclusion period following previous interventional research involving the human person, if applicable

Trial design

630 participants in 3 patient groups

Subset 1

Description:

Decompensated cirrhosis as primary diagnosis, irrespective of liver disease etiology

Treatment:

Other: Standardized assessments and biobanking

Subset 2

Description:

Other chronic end-stage liver diseases requiring LT, listed under MELD offering schemes, including notably but not exclusively cholestatic diseases, primary biliary cholangitis, primary sclerosing cholangitis

Treatment:

Other: Standardized assessments and biobanking

Subset 3

Description:

Hepato-cellular carcinoma as primary diagnosis, whatever the etiology of the underlying liver disease with or without underlying cirrhosis

Treatment:

Other: Standardized assessments, guided tumor biopsy and biobanking