LEOPARD Prospective Validation Cohort 1

Официальное название

Validation of LEOPARD Predictive Models of Delisting in Liver Transplant Candidates: the LEOPARD Longitudinal Multicentre Prospective Validation Cohort 1, With Bio- and Tissue Collection

Обзор

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.

Вмешательства

• Другое Standardized assessments, guided tumor biopsy and biobanking
  Standardized assessment of Scores * Guided tumor biopsy in patients listed for hepatocellular carcinoma with active tumor at listing in centers not perfoming tumor biopsy on a routine basis * Additional blood sampling for biobanking and subsequent analysis of innovative biomarkers and OMICs * Urine sampling for biobanking and subsequent analysis of innovative biomarkers * Ascite sampling for biobanking and subsequent analysis * Tumor sampling for biobanking and subsequent analysis * Centralized
• Другое Standardized assessments and biobanking
  * Standardized assessment of Scores * Additional blood sampling for biobanking and subsequent analysis of innovative biomarkers and OMICs * Urine sampling for biobanking and subsequent analysis of innovative biomarkers * Ascite sampling for biobanking and subsequent analysis * Tumor sampling for biobanking and subsequent analysis * Centralized assay for routine biomarkers

Первичные конечные точки

• Clinical primary endpoint will be a composite of mortality or drop out for being too sick on transplantation waiting list, since kinetics of dropout differs according to LT indications [Срок оценки: 3 months after listing in subsets 1 & 2 ; 12 months after listing in subset 3]

Вторичные конечные точки (11)

• Number of participants with 6-month mortality/dropout for being too sick (subsets 1 to 3) [Срок оценки: 6 months after listing]
• Number of participants with 9-month mortality/dropout for too sick in subsets 1, 2 [Срок оценки: 9 months after listing]
• Number of participants with 12-month mortality/dropout for too sick in subset 3 [Срок оценки: 12 months after listing]
• Causes of death/drop-out for being too sick [Срок оценки: 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 [Срок оценки: From date of inclusion until date of delisting for patient's decision or clinical improvement, assessed up to12 months]
• Time from listing to death/drop-out [Срок оценки: 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 [Срок оценки: From date of listing until date of transplantation, assessed up to 12 months]
• Number of participants with 1-year post transplant survival in subsets 1-2 [Срок оценки: 12 months after liver transplantation]
• Number of participants with 9-month HCC recurrence in subset 3 [Срок оценки: 9 months after liver transplantation]
• Number of participants with 9-month post transplant survival in subset 3 [Срок оценки: 9 months after liver transplantation]
• 9-month and 12-month transplant benefit in subsets 3 and 1-2, respectively [Срок оценки: 9 months and 12 months after liver transplantation]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 4 центра

• Beaujon Hospital, Department of Hepatology — Clichy
• Hospital Henri Mondor, Department of Hepatology — Créteil
• St Eloi Hospital, Department of Hepato-gastro-enterology, — Montpellier
• Hospital La Pitié Salpêtrière, Department of Hepato-gastro-enterology — Paris

Бельгия · 1 центр

• Department of Gastroenterology and Hepatology Universitair Ziekenhuis Gent — Ghent

Германия · 1 центр

• Universitätsklinikum Schleswig - Holstein | UKSH · Transplantation Medicine — Kiel

Италия · 1 центр

• Italian National Transplant Center — Roma

Нидерланды · 1 центр

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

Идентификаторы

NCT: NCT06723275 · APHP231778 · 2024-A00808-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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