New Prognostic Predictive Models of Mortality of Decompensated Cirrhotic Patients Waiting for Liver Transplantation (SUPERMELD)

Construction of New Predictive Mathematical Models of Mortality in Decompensated Cirrhotic Patients Who Are Candidates for Liver Transplantation

The MELD score is a predictive model of cirrhosis mortality used in France since 2007 to prioritize access to liver transplantation for patients enrolled in the national waiting list. The predictive value of this score was recently revised downward with a C index of the order of 0.65-0.67 and 20% of the patients enrolled for decompensated cirrhosis have access to liver transplantation by a subjective system of "expert component" independent of the MELD because of this lack of precision. The use of the MELD score to individually define access to the transplant should so be reconsidered. Recently new predictive models of cirrhosis mortality better than MELD have been developed and new mortality predictors independent of MELD have been published.

The goal of this study is to design prognostic predictive models of mortality for decompensated cirrhotic patients enrolled on the national liver transplant waiting list including known (MELD, MELD Na) as more recent (CLIF-C AD, CLIF - CACLF) predictive models and new objective predictors studied in combination in order to optimize the system of allocation of hepatic allografts in France.

The expected benefits of this search are twofold:

• At the individual level: The possibility for patients at high risk of death but with intermediate MELD score to be transplanted.

• Public health plan:

  • Improving the equity of graft allocation system.
  • Decreased mortality in the waiting list by improving the fairness and efficiency of the graft allocation system, a major public health issue

Study Overview

• Status: Recruiting
• Conditions: Decompensated Cirrhosis; Liver Transplantation
• Intervention / Treatment: Other: SuperMELD

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christophe Duvoux, PHD; Phone Number: +33 01 49 81 43 28; Email: christophe.duvoux@aphp.fr

Study Locations

• France
  • Créteil, France, 94000
    • Recruiting
    • Pr Duvoux
    • Contact: Christophe Duvoux, PhD; Phone Number: +33 0149814328; Email: christophe.duvoux@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (≥18 years old) newly registered on national waiting list with main diagnosis "cirrhosis"
• Patients enrolled on the national waiting list under the "national liver score" allocation scheme whether an expert component is considered or not
• Patients (or trusted person or family member or close relation if the patient is unable to express consent) who have been informed and signed their informed consent
• Patients affiliated to a health insurance scheme

Exclusion Criteria:

• Patients enrolled with decompensated cirrhosis associated with hepatocellular carcinoma
• Patients on AVK (INR and therefore MELD and CLIF scores uninterpretable)
• Vulnerable population (person under guardianship or curatorship or deprived of liberty by a judicial decision)
• Pregnant and / or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: SuperMELD	Other: SuperMELD; The population of this arm will consist of patients newly enrolled in the National Liver Transplantation Waiting List for decompensated cirrhosis, whose liver function and MELD score are assessed at enrollment and then routinely reassessed at least quarterly during the waiting phase. Patients will be followed from their listing to transplantation or discharge or death.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predictive value of the new multivariate prognostic models in patients listed for decompensated cirrhosis	Predictive value of mortality and drop out in the waiting list	Month 3.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual predictive value of each of the new candidate predictors	CRP, copeptin, NT-pro BNP, vitamin D, leucocytes, PMN/lymphocytes ratio, urinary NGal, cystatin C, frailty index, sarcopenia (abdominal tomodensitometry to measure the surface of psoas), caloric intake, encephalopathy (ammonia level, stroop application), and transferrin.	Month 3. Month 6, Month 9, Month 12Month 12
Complications predicted by each of the independent predictors	infection, renal dysfunction, encephalopathy, bleeding, ACLF	Month 3 Month 6, Month 9, Month 12.Month 12
Added predictive value for mortality and drop out of new multivariate prognostic models on MELD (model end stage for liver disease)		Months 3, Month 6, Month 9, Month 12.
Evaluation of the predictive value of the CLIF (Chronic LIver Failure)-C (cirhosis) AD (Decompensation) score in decompensated cirrhotics listed without organ failure	death and drop out	Months 3, Month 6, Month 9, Month 12.

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Candy Estevez, APHP DRCI; Study Chair: Laetitia Gregoire, APHP URC

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: January 18, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: May 2, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Liver transplantation; Predictive prognostic models; Decompensated cirrhosis
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis
• Other Study ID Numbers: K170914J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No