Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure: iNdications and outComEs

Liver Cirrhosis Clinical Trial

— CHANCE  

Official title:

Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure (ACLF): iNdications and outComEs

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04613921
• Other study ID #: 2020/01325
• Status: Recruiting
• Start date: July 8, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2023
• Source: European Foundation for Study of Chronic Liver Failure
• Contact: Anna Bosch
• Phone: 34 93 227 1400
• Email: anna.bosch[@]efclif.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Management of ACLF is mainly supportive. The poor outcomes lead physicians to consider liver transplantation as an option, even if controversial. In sicker recipients, LT results in immediate survival, but poor medium-term survival rates in some studies. The scarcity of deceased donors obliges to maximize LT success. Alternative strategies, as living-donor LT, should be explored. LDLT has impressive results in Eastern centers, but it is restrained in Western countries, due to potential life-threatening complications in the donor.

Description:

The aim of this study is to compare 1-year graft and patient survival rates after liver transplantation (LT) in patients with ACLF-2 or 3 at the time of LT, with patients with decompensated cirrhosis without ACLF-2 or 3 at the time of LT and also with transplant-free survival of patients with ACLF-2 or 3 not listed for LT. Secondary objectives are as follows: - To assess the proportion of patients with ACLF-2 or 3 referred to transplant team who are listed or not and reasons of this decision. - To evaluate the outcomes of patients listed with ACLF-2 or 3 on the waiting list compared with those of patients listed with decompensated cirrhosis without ACLF-2 or 3. - To define independent predictive factors of death/delisting on the waiting list for patients listed with ACLF-2 or 3 and develop a new prognostic model based on ACLF criteria to predict mortality on the waiting list and to improve the allocation of organs. - To compare the characteristics of accepted grafts for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3 and their impact on post-LT outcomes. - To explore independent predictive factors of death after LT for patients transplanted with ACLF-2 or 3 to design futility criteria for LT. - To compare post-LT survival rates of patients with ACLF-2 or 3 at listing and patients without ACLF at listing who develop ACLF-2 or 3 on the waiting list. - To compare post-LT quality of life (QoL) for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 1. Male or female subject =18 years of age.

2. Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology).

3. Subjects who have been hospitalized for acute decompensation of liver cirrhosis and

referred to the transplant team:

• Group 1: patients listed for liver transplantation with ACLF-2 or 3 at the time of listing or developing ACLF 2-3 while on the waiting list.
• Group 2: patients listed for liver transplantation with decompensated cirrhosis without ACLF-2 or 3 and poor liver function (MELD>20) at the time of listing.
• Group 3: patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation.

4. Patients (or trusted person, family member or close relation if the patient is unable to express consent) who have been informed and signed their informed consent Inclusion criteria Exclusion Criteria: -

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Fibrosis
• Hepatic Insufficiency
• Liver Cirrhosis
• Liver Diseases
• Liver Failure
• Liver Transplant; Complications

Intervention

Other:
• Observational Protocol
The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)

Locations

Country	Name	City	State
Argentina	Austral University Hospital	Buenos Aires
Argentina	Hospital Alemán	Buenos Aires
Argentina	Italian Hospital in Buenos Aires	Buenos Aires
Australia	Austin Hospital	Heidelberg
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Royal Prince Alfred Hospital	Sydney
Austria	Medical University of Vienna, Department of Transplant Surgery	Wien
Belgium	CUB Erasme Hospital	Brussels
Belgium	Ghent University Hospital	Ghent
Belgium	UZ Leuven	Leuven
Brazil	Walter Cantídio University Hospital	Fortaleza
Brazil	Irmandade Santa Casa de Misericórdia de Porto Alegre	Porto Alegre
Brazil	Hospital das Clínicas da Universidade de São Paulo	São Paulo
Canada	University of Alberta	Edmonton
Canada	University of Toronto, Multiorgan Transplant Program	Toronto
Colombia	Pablo Tobón Uribe Hospital	Medellín
Czechia	Institute for Clinical and Experimental Medicine	Praha
France	APHP Beaujon	Clichy
France	APHP Henri Mondor	Créteil
France	Hôpital de la Croix-Rousse	Lyon
France	CHU Montpellier-Hôpital Saint Eloi	Montpellier
France	APHP Hôpitaux Universitaires Pitié Salpêtrière	Paris
France	CHU Rennes, Hôpital De Pontchaillou	Rennes
France	Hautepièrre Hospital, Service de Réanimation Médicale	Strasbourg
France	Trousseau Hospital,	Tours
France	Hôpital Paul Brousse	Villejuif
Germany	University Hospital Aachen	Aachen
Germany	Charité University Hospital	Berlin
Germany	Goethe University Clinic	Frankfurt
Germany	University Medical Center, Hamburg Eppendorf	Hamburg
Germany	Hannover Medical School	Hannover
Germany	University Hospital Heidelberg	Heidelberg
Germany	Jena University Hospital	Jena
Germany	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel
Germany	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel	Schleswig-Holstein
Germany	Leipzig University Hospital	Leipzig
Germany	University Hospital Mainz	Mainz
Germany	LMU Großhadern	Munich
Germany	UKM Muenster	Münster
Germany	University Hospital Regensburg	Regensburg	Eastern Bavaria
Germany	University Hospital Tübingen	Tübingen
Hong Kong	Queen Mary Hospital, The University of Hong Kong	Hong Kong
India	Aster CMI Hospital	Bengaluru	Karnataka
India	Dr.Rela Institute & Medical Centre	Chennai
India	Fortis Hospital Noida, FEHI, FMRI	Gurugramam
India	Medanta Medicity	Gurugramam
India	Mahatma Gandhi University of Medical Sciences and Technology	Jaipur	Rajasthan
India	Amrita Institute of Medical Sciences	Kochi
India	Global Hospital. Super speciality & transplant centre	Mumbai
India	Kasturba Hospital	Mumbai	Maharashtra
India	Seth GSMC & KEM Hospital	Mumbai	Maharashtra
India	Indraprastha Apollo Hospitals	New Delhi	Delhi
India	Max Saket Hospital	New Delhi
India	Yashoda Hospitals	Secunderabad
Italy	Ospedale Papa Giovanni XXIII-	Bergamo
Italy	S.Orsola Hospital - Alma Mater Studiorum University of Bologna	Bologna
Italy	Ca' Granda. Policlinico Milano	Milan
Italy	Niguarda Hospital	Milan
Italy	University and Hospital of Padova	Padova
Japan	Kyushu University Hospital	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kyoto University Hospital	Kyoto
Japan	Nagasaki University Hospital	Nagasaki
Japan	Tokyo University Hospital	Tokyo
Korea, Republic of	Samsung Medical Center	Seoul
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Mexico City
Netherlands	University Medical Center Groningen (UMCG)	Groningen
Netherlands	Erasmus MC University Medical Center	Rotterdam
New Zealand	Auckland City Hospital- New Zealand Liver Transplant Unit	Auckland
Poland	Medical University of Warsaw, Dept. of General, Transplant & Liver Surgery	Warsaw
Portugal	Hospital Curry Cabral	Lisboa
Spain	Hospital Clinic in Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Sweden	Karolinska Institutet	Stockholm
Switzerland	Geneva University Hospital (HUG)	Geneva
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Turkey	Istanbul Memorial Bahcelievler Hospital	Istanbul
Turkey	Inonu University, Liver Transplantation Institute	Malatya	Anatolia
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	Scottish Liver Transplant Unit, Royal Infirmary	Edinburgh
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	King's College Hospital	London
United Kingdom	Royal Free Hospital	London
United States	Piedmont Healthcare	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The University of Chicago Medicine	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Baylor College of Medicine (Scott & White)	Dallas	Texas
United States	Baylor St. Luke's Medical Centre	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	Cedars-Sinai Comprehensive Transplant Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Montefiore Medical Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Utah Health	Salt Lake City	Utah
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
European Foundation for Study of Chronic Liver Failure

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  France,  Germany,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (3)

Artru F, Louvet A, Ruiz I, Levesque E, Labreuche J, Ursic-Bedoya J, Lassailly G, Dharancy S, Boleslawski E, Lebuffe G, Kipnis E, Ichai P, Coilly A, De Martin E, Antonini TM, Vibert E, Jaber S, Herrerro A, Samuel D, Duhamel A, Pageaux GP, Mathurin P, Saliba F. Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in acute-on-chronic liver failure grade 3. J Hepatol. 2017 Oct;67(4):708-715. doi: 10.1016/j.jhep.2017.06.009. Epub 2017 Jun 21. — View Citation

Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, Laleman W, Trebicka J, Elkrief L, Hopf C, Solis-Munoz P, Saliba F, Zeuzem S, Albillos A, Benten D, Montero-Alvarez JL, Chivas MT, Concepcion M, Cordoba J, McCormick A, Stauber R, Vogel W, de Gottardi A, Welzel TM, Domenicali M, Risso A, Wendon J, Deulofeu C, Angeli P, Durand F, Pavesi M, Gerbes A, Jalan R, Moreau R, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium. Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology. 2015 Jul;62(1):243-52. doi: 10.1002/hep.27849. Epub 2015 May 29. — View Citation

Sundaram V, Jalan R, Wu T, Volk ML, Asrani SK, Klein AS, Wong RJ. Factors Associated with Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation. Gastroenterology. 2019 Apr;156(5):1381-1391.e3. doi: 10.1053/j.gastro.2018.12.007. Epub 2018 Dec 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	survival	1 year