October 04, 2023 The CHANCE Steering Committee meets online to review preliminary data and the status of patient recruitment As the CHANCE study is approaching the 1000th patient milestone, members of the CHANCE Steering Committee and Management Team met online to review preliminary data and discuss about the state of play with regard to patient recruitment.

BARCELONA—The CHANCE Steering Committee Meeting was held online on 3 October 2023 to review the in-depth patient follow-up assessment carried out by EF CLIF Data Managers and Statisticians over the last few months and to foster discussion around the available data against the primary and secondary endpoints of the study.

The meeting was chaired and presented by Rajiv Jalan, Professor of Hepatology at University College London (UK), Scientific Director at EF CLIF (Spain), and Coordinator of the CHANCE study; and counted with the participation of CHANCE Principal Investigator Thierry Gustot (CUB Hôpitla Erasme, Belgium); Co-Principal Investigators William Bernal (King’s College Hospital, UK) and Javier Fernández (Hospital Clínic de Barcelona, Spain); Anna Bosch, General Manager of EF CLIF; Cristina Sánchez-Garrido, Head of the Data Managent Center at EF CLIF; Carlos de la Peña-Ramírez, Statistician at EF CLIF; Juan Manuel Díaz, Data Manager at EF CLIF; Yolanda Godoy, Scientific Assistant at EF CLIF; Lidia Garcia-Campmany, Scientific Communications Manager at EF CLIF; CHANCE Scientific Advisory Board member Christophe Duvoux for and on behalf of the European Society for Organ Transplantation (ESOT); and regional coordinators Adrian Gadano (Latin America), Ruben Hernaez (North America), Laure Elkrief (France), Wojciech Polak (The Netherlands, Poland, Czech Republic, Denmark, Sweden), Christian Toso (Switzerland), Giovanni Perricone on behalf of Luca Belli (Italy), and Takanobu Hara on behalf of Susumu Eguchi (Japan).

Putting liver transplantation into perspective, Rajiv Jalan discussed the potential role of liver transplantation in acute-on-chronic liver failure (ACLF) and how the model for end-stage liver disease (MELD), currently used to assign priority to most liver transplant candidates age 12 and older, falls short in estimating risk of death of patients with ACLF on the waiting list. Although the MELD score is driving the allocation of grafts in many countries, the final decision for allocation is frequently based on multiple parameters besides MELD including donor–recipient matching, and local or regional priorities. Risk factors of high mortality after liver transplantation in patients with severe ACLF (grades 2 and 3) include severe comorbidities, acute respiratory distress syndrome, high vasopressor requirement, severe lactatemia, sepsis, time on the waiting list and transplantation using marginal organs. All together, these observations served the basis for the design of the CHANCE study and formulation of primary, secondary and exploratory objectives. The overarching objective is to compare 1-year graft and patient survival rates post-liver transplantaton in patients with ACLF grades 2 or 3 at the time of liver transplantation with patients with decompensated cirrhosis without ACLF, and transplant-free survival of patients with ACLF grades 2 or 3 not listed for liver transplantation with the aim to issue consensus recommendations on the management of ACLF and prioritization on waiting list for liver transplantation.

Jalan presented an overview of patient recruitment and some promising preliminary data from interim analyses. The global scope of the CHANCE study comes with many challenges that he also discussed. The focus was on ensuring all clinical data are collected accurately, data cleaning and completing follow-up visits - key requirements to be able to provide answers to primary and secondary endpoints. At this stage of the study, Jalan emphasized the need to develop strategies for maximizing the impacts of CHANCE research outputs and the possibility to carry out future ancillary studies.

About the CHANCE study

CHANCE is a multicenter, global, observational study designed to assess the benefit of liver transplantation in patients with acute-on-chronic liver failure (ACLF) grade 2 or grade 3. This study counts with the support of the International Liver Transplantation Society (ILTS) and the European Liver and Intestine Transplant Association (ELITA) to recruit 2000 patients in 80 centers in 27 countries around the world. The primary objective of the CHANCE study is to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF grade 2 or grade 3 at the time of liver transplantation with patients with decompensation of cirrhosis without ACLF-2 or 3 and transplant-free survival of patients with ACLF-2 or 3 not listed for liver transplantation. The international nature of this study will allow for deep assessments of the potential impact of different precipitating factors of ACLF (e.g., alcohol vs. Hepatitis B virus flare), different types of liver transplantation (deceased donor vs. living donor liver transplantation) and different regional and national allocation systems on transplant outcomes. Beside these clinical objectives, the CHANCE study aims to build a repository of biological samples to explore new biomarkers to predict prognosis on the waiting list and after liver transplantation, and mechanisms of liver and extrahepatic organ recovery.

ClinicalTrials.gov Identifier: NCT04613921