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

Sponsor

European Foundation for Study of Chronic Liver Failure (Other)

Overall Status

Recruiting

CT.gov ID

NCT04613921

Collaborator

(none)

3,000

Enrollment

Locations

65.8

Anticipated Duration (Months)

30.9

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Liver Diseases Liver Cirrhosis Acute-On-Chronic Liver Failure Liver Transplant; Complications	Other: Observational Protocol

Detailed 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

3000 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jul 8, 2021

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
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 (n=2,000)	Other: Observational Protocol The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)
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 (n=500)	Other: Observational Protocol The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)
Group 3 patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation (n=500)	Other: Observational Protocol The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)

Arm

Intervention/Treatment

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 (n=2,000)

Other: Observational Protocol

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

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 (n=500)

Other: Observational Protocol

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

Group 3

patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation (n=500)

Other: Observational Protocol

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

Outcome Measures

Primary Outcome Measures

Survival [1 year]
survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

1. Male or female subject ≥18 years of age.

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

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:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Comprehensive Transplant Center	Los Angeles	California	United States	90048
2	University of Colorado	Aurora	Colorado	United States	80045
3	Tampa General Hospital	Tampa	Florida	United States	33606
4	Piedmont Healthcare	Atlanta	Georgia	United States	30309
5	The University of Chicago Medicine	Chicago	Illinois	United States	60637
6	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
7	Weill Cornell Medicine	New York	New York	United States	10021
8	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029-5674
9	Cleveland Clinic	Cleveland	Ohio	United States	44195
10	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
11	Baylor College of Medicine (Scott & White)	Dallas	Texas	United States	75246
12	Michael E DeBakey VA Medical Center	Houston	Texas	United States	77030-4211
13	Baylor St. Luke's Medical Centre	Houston	Texas	United States	77030
14	University of Utah Health	Salt Lake City	Utah	United States	84132
15	Austral University Hospital	Buenos Aires		Argentina
16	Hospital Alemán	Buenos Aires		Argentina
17	Italian Hospital in Buenos Aires	Buenos Aires		Argentina
18	Austin Hospital	Heidelberg		Australia
19	Sir Charles Gairdner Hospital	Nedlands		Australia
20	Royal Prince Alfred Hospital	Sydney		Australia
21	Medical University of Graz	Graz		Austria
22	Medical University of Vienna, Department of Transplant Surgery	Wien		Austria
23	CUB Erasme Hospital	Brussels		Belgium
24	Ghent University Hospital	Ghent		Belgium
25	UZ Leuven	Leuven		Belgium
26	Walter Cantídio University Hospital	Fortaleza		Brazil
27	Irmandade Santa Casa de Misericórdia de Porto Alegre	Porto Alegre		Brazil
28	Hospital das Clínicas da Universidade de São Paulo	São Paulo		Brazil
29	University of Alberta	Edmonton		Canada
30	University of Toronto, Multiorgan Transplant Program	Toronto		Canada
31	Pablo Tobón Uribe Hospital	Medellín		Colombia
32	Institute for Clinical and Experimental Medicine	Praha		Czechia
33	APHP Beaujon	Clichy		France
34	APHP Henri Mondor	Créteil		France
35	Hôpital de la Croix-Rousse	Lyon		France
36	CHU Montpellier-Hôpital Saint Eloi	Montpellier		France
37	APHP Hôpitaux Universitaires Pitié Salpêtrière	Paris		France
38	CHU Rennes, Hôpital De Pontchaillou	Rennes		France
39	Hautepièrre Hospital, Service de Réanimation Médicale	Strasbourg		France
40	Trousseau Hospital,	Tours		France
41	Hôpital Paul Brousse	Villejuif		France
42	University Hospital Aachen	Aachen		Germany
43	Charité University Hospital	Berlin		Germany
44	Goethe University Clinic	Frankfurt		Germany
45	University Medical Center, Hamburg Eppendorf	Hamburg		Germany
46	Hannover Medical School	Hannover		Germany
47	University Hospital Heidelberg	Heidelberg		Germany
48	Jena University Hospital	Jena		Germany
49	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel		Germany
50	Leipzig University Hospital	Leipzig		Germany
51	University Hospital Mainz	Mainz		Germany
52	LMU Großhadern	Munich		Germany
53	UKM Muenster	Münster		Germany
54	University Hospital Tübingen	Tübingen		Germany
55	Queen Mary Hospital, The University of Hong Kong	Hong Kong		Hong Kong
56	Dr.Rela Institute & Medical Centre	Chennai		India
57	Fortis Hospital Noida, FEHI, FMRI	Gurugramam		India
58	Medanta Medicity	Gurugramam		India
59	Amrita Institute of Medical Sciences	Kochi		India
60	Global Hospital. Super speciality & transplant centre	Mumbai		India
61	Max Saket Hospital	New Delhi		India
62	Yashoda Hospitals	Secunderabad		India
63	Ospedale Papa Giovanni XXIII-	Bergamo		Italy
64	S.Orsola Hospital - Alma Mater Studiorum University of Bologna	Bologna		Italy
65	Ca' Granda. Policlinico Milano	Milan		Italy
66	Niguarda Hospital	Milan		Italy
67	University and Hospital of Padova	Padova		Italy
68	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy
69	Kyushu University Hospital	Fukuoka		Japan
70	Hiroshima University Hospital	Hiroshima		Japan
71	Kyoto University Hospital	Kyoto		Japan
72	Nagasaki University Hospital	Nagasaki		Japan
73	Tokyo University Hospital	Tokyo		Japan
74	Samsung Medical Center	Seoul		Korea, Republic of
75	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Mexico City		Mexico
76	University Medical Center Groningen (UMCG)	Groningen		Netherlands
77	Erasmus MC University Medical Center	Rotterdam		Netherlands
78	Auckland City Hospital- New Zealand Liver Transplant Unit	Auckland		New Zealand
79	Guillermo Almenara National Hospital	Lima		Peru
80	Medical University of Warsaw, Dept. of General, Transplant & Liver Surgery	Warsaw		Poland
81	Hepato-Biliary-Pancreatic and Transplantation Centre	Lisboa		Portugal
82	Hospital Curry Cabral	Lisboa		Portugal
83	Hospital Clinic in Barcelona	Barcelona		Spain
84	Hospital Vall d'Hebron	Barcelona		Spain
85	Hospital Universitario 12 de Octubre	Madrid		Spain
86	Hospital Universitario Ramón y Cajal	Madrid		Spain
87	Hospital Marqués de Valdecilla	Santander		Spain
88	Hospital Universitario Virgen del Rocío	Sevilla		Spain
89	Hospital Universitari i Politècnic La Fe	Valencia		Spain
90	Geneva University Hospital (HUG)	Geneva		Switzerland
91	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
92	Istanbul Memorial Bahcelievler Hospital	Istanbul		Turkey
93	Queen Elizabeth Hospital Birmingham	Birmingham		United Kingdom
94	Scottish Liver Transplant Unit, Royal Infirmary	Edinburgh		United Kingdom
95	Leeds Teaching Hospitals NHS Trust	Leeds		United Kingdom
96	King's College Hospital	London		United Kingdom
97	Royal Free Hospital	London		United Kingdom