Clinical trial NCT04613921: Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure: iNdications and outComEs
Official title: Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure (ACLF): iNdications and outComEs
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Liver Diseases
Liver Cirrhosis
Acute-On-Chronic Liver Failure
Liver Transplant; Complications
Lead sponsor: European Foundation for Study of Chronic Liver Failure
Sponsor class: OTHER
First posted: 2020-11-03
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acute or subacute liver failure. Patients with hepatocellular carcinoma Subjects listed for transplantation other than liver or liver-kidney transplant.

Subjects with previous liver transplantation. Vulnerable population. Pregnant and/or breastfeeding woman Patients with relevant comorbidities

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.

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.

Eligibility criteria: 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:

-

Primary outcomes:
measure: Survival
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Transplant Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor College of Medicine (Scott & White)
state: Texas
city: Houston
country: United States
facility: Michael E DeBakey VA Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Centre
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Buenos Aires
country: Argentina
facility: Austral University Hospital
city: Buenos Aires
country: Argentina
facility: Hospital Alemán
city: Buenos Aires
country: Argentina
facility: Italian Hospital in Buenos Aires
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
city: Wien
country: Austria
facility: Medical University of Vienna, Department of Transplant Surgery
city: Brussels
country: Belgium
facility: CUB Erasme Hospital
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Fortaleza
country: Brazil
facility: Walter Cantídio University Hospital
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericórdia de Porto Alegre
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Universidade de São Paulo
city: Edmonton
country: Canada
facility: University of Alberta
city: Toronto
country: Canada
facility: University of Toronto, Multiorgan Transplant Program
city: Medellín
country: Colombia
facility: Pablo Tobón Uribe Hospital
city: Praha
country: Czechia
facility: Institute for Clinical and Experimental Medicine
city: Clichy
country: France
facility: APHP Beaujon
city: Créteil
country: France
facility: APHP Henri Mondor
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Montpellier
country: France
facility: CHU Montpellier-Hôpital Saint Eloi
city: Paris
country: France
facility: APHP Hôpitaux Universitaires Pitié Salpêtrière
city: Rennes
country: France
facility: CHU Rennes, Hôpital De Pontchaillou
city: Strasbourg
country: France
facility: Hautepièrre Hospital, Service de Réanimation Médicale
city: Tours
country: France
facility: Trousseau Hospital,
city: Villejuif
country: France
facility: Hôpital Paul Brousse
city: Regensburg
country: Germany
facility: University Hospital Regensburg
state: Eastern Bavaria
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH)
state: Schleswig-Holstein
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Berlin
country: Germany
facility: Charité University Hospital
city: Frankfurt
country: Germany
facility: Goethe University Clinic
city: Hamburg
country: Germany
facility: University Medical Center, Hamburg Eppendorf
city: Hannover
country: Germany
facility: Hannover Medical School
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Jena
country: Germany
facility: Jena University Hospital
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH)
city: Leipzig
country: Germany
facility: Leipzig University Hospital
city: Mainz
country: Germany
facility: University Hospital Mainz
city: Munich
country: Germany
facility: LMU Großhadern
city: Münster
country: Germany
facility: UKM Muenster
city: Tübingen
country: Germany
facility: University Hospital Tübingen
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital, The University of Hong Kong
city: New Delhi
country: India
facility: Indraprastha Apollo Hospitals
state: Delhi
city: Bengaluru
country: India
facility: Aster CMI Hospital
state: Karnataka
city: Mumbai
country: India
facility: Kasturba Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Seth GSMC & KEM Hospital
state: Maharashtra
city: Jaipur
country: India
facility: Mahatma Gandhi University of Medical Sciences and Technology
state: Rajasthan
city: Chennai
country: India
facility: Dr.Rela Institute & Medical Centre
city: Gurugramam
country: India
facility: Fortis Hospital Noida, FEHI, FMRI
city: Gurugramam
country: India
facility: Medanta Medicity
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences
city: Mumbai
country: India
facility: Global Hospital. Super speciality & transplant centre
city: New Delhi
country: India
facility: Max Saket Hospital
city: Secunderabad
country: India
facility: Yashoda Hospitals
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII-
city: Bologna
country: Italy
facility: S.Orsola Hospital - Alma Mater Studiorum University of Bologna
city: Milan
country: Italy
facility: Ca' Granda. Policlinico Milano
city: Milan
country: Italy
facility: Niguarda Hospital
city: Padova
country: Italy
facility: University and Hospital of Padova
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Tokyo
country: Japan
facility: Tokyo University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
city: Rotterdam
country: Netherlands
facility: Erasmus MC University Medical Center
city: Auckland
country: New Zealand
facility: Auckland City Hospital- New Zealand Liver Transplant Unit
city: Warsaw
country: Poland
facility: Medical University of Warsaw, Dept. of General, Transplant & Liver Surgery
city: Lisboa
country: Portugal
facility: Hospital Curry Cabral
city: Barcelona
country: Spain
facility: Hospital Clinic in Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Geneva
country: Switzerland
facility: Geneva University Hospital (HUG)
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Malatya
country: Turkey
facility: Inonu University, Liver Transplantation Institute
state: Anatolia
city: Istanbul
country: Turkey
facility: Istanbul Memorial Bahcelievler Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Edinburgh
country: United Kingdom
facility: Scottish Liver Transplant Unit, Royal Infirmary
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References:
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.
citation: 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.
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.