Predicting Acute-on-Chronic Liver Failure in Cirrhosis (PREDICT) Study (PREDICT)

The aim of this study is to assess prospectively the critical period prior to the development of Acute-on-Chronic Liver Failure (ACLF) (1), to uncover mechanistic and pathophysiological processes associated with the development and clinical course of ACLF (2) and to identify the precipitating events of ACLF (3).

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis With Acute Decompensation
• Intervention / Treatment: Other: Observation protocol

Detailed Description

1. This International-European, investigator-initiated, multicenter, prospective, observational study will be performed in centers that belong to the European Foundation for the Study of Chronic Liver failure (EF-CLIF)-European Association for Study of the Liver (EASL)-EASL-CLIF Consortium.
2. The population of patients would include ca. 1,200 cirrhotic patients over a twelve-months period. These patients will be admitted/referred to the study center because of acute decompensation (AD) of cirrhosis (ascites, overt encephalopathy, GI-hemorrhage, new onset of non-obstructive jaundice and/or bacterial infections), without ACLF (as defined according to the Canonic study ) at hospitalization.
3. After the enrolment visit, the patients will be stratified into two groups: Group 1 patients with high risk of ACLF development (CLIF-C AD score ≥ 50) and in Group 2 patients with low risk of ACLF (CLIF-C AD score <50). The whole cohort will be followed for 3 months, while Group 1 will be followed more closely. Development of ACLF is an end-point and in this case a final visit 7-10 days after ACLF development is planned. Data on liver transplantation, mortality and causes of mortality 3 months, 6 months and 12 months will be collected in the whole cohort.
4. Prospective collection of biological material and performance of ancillary studies investigating predictors for development and pathogenesis of ACLF.

Specific goals of the study:

• To identify early clinical predictors, biomarkers, mechanisms and precipitating events during the critical period prior to and involved in the development and clinical course of ACLF (with special emphasis to medical trajectory and drug history) in patients admitted/referred to study center with acute decompensation of cirrhosis (ascites, GI-hemorrhage, overt encephalopathy, new onset of non-obstructive jaundice and/or bacterial infections) and the chronological relationship of the events with occurrence and dynamics of ACLF development.
• To develop a score predicting ACLF development (CLIF-PREDICT score) and assess 28-day, 90-day, 6-month and 1-year all-cause mortality in cirrhotic patients with acute AD, but without ACLF.
• To serve as a core (hub) study for prospective ancillary studies regarding diagnosis, prognosis and pathogenesis of AD and ACLF.

Main endpoints

• Assessment of the critical period prior to ACLF development

  • Characterization of mechanisms responsible for ACLF development
  • Predictors of clinical course dynamics of ACLF evolution and mortality.
  • Identification and role of precipitating events for ACLF development.
• To elaborate a CLIF-PREDICT score 2. Secondary endpoints
• Prospective core ancillary studies to investigate the pathogenesis of ACLF.

• Study Type: Observational
• Enrollment (Actual): 1314

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medical University Graz
  • Innsbruck, Austria
    • Medical University of Innsbruck
  • Vienna, Austria
    • Medical University of Vienna
• Belgium
  • Antwerp, Belgium
    • University Hospital Antwerp
  • Brussels, Belgium
    • C.U.B Erasmo
  • Ghent, Belgium
    • Ghent University Hospital
  • Leuven, Belgium
    • University Hospital Leuven
• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Hvidovre University Hospital
• France
  • Bondy, France
    • Hospital Jean Verdier
  • Paris, France
    • Hopital Beaujon
  • Paris, France
    • Hopital Paul Brousse
• Germany
  • Aachen, Germany
    • RTWH Aachen
  • Bonn, Germany
    • University Hospital Bonn
  • Frankfurt am Main, Germany
    • JW Goethe University Hospital
  • Halle, Germany
    • University Hospital Halle-Wittenberg
  • Hannover, Germany
    • Hannover Medical School
  • Jena, Germany
    • University Hospital Jena
  • Leipzig, Germany
    • University Hospital Leipzig
  • Munich, Germany
    • University hospital Munich LMU
• Hungary
  • Debrecen, Hungary
    • University of Debrecen
• Italy
  • Bologna, Italy
    • University of Bologna
  • Brindisi, Italy
    • Internal Medicine PO Ostuni
  • Padova, Italy
    • University Clinic Padova
  • Rome, Italy
    • Università Sapienza
  • Torino, Italy
    • A.O.U. Torino
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
• Portugal
  • Vila Real, Portugal
    • CHTMAD Vila Real
• Slovakia
  • Kosice, Slovakia
    • Pavol Jozef Sfarik University Kosice/Roosevelt Hospital Bystrica
• Spain
  • Barcelona, Spain
    • Hospital de Sant Pau
  • Barcelona, Spain
    • Hospital Universitari Vall d´Hebron
  • Barcelona, Spain
    • Hospital Clinic y Provencial de Barcelona
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Sevilla, Spain
    • Virgen del Rocío
• Switzerland
  • Bern, Switzerland
    • Inselspital
  • Geneva, Switzerland
    • Hôpitaux Universitaires Genève
  • St. Gallen, Switzerland
    • Cantonal Hospital St. Gallen
• Turkey
  • Istanbul, Turkey
    • Marsara University
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham University Hospitals
  • London, United Kingdom
    • Royal Free Hospital
  • London, United Kingdom
    • Imperial College
  • London, United Kingdom
    • King´s College
  • Nottingham, United Kingdom
    • Nottingham University Hospitals
  • Plymouth, United Kingdom
    • Derriford Hospital, Plymouth Hospitals Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The population of patients would include ca. 1,200 cirrhotic patients over a twelve-months period. These patients will be admitted/referred to the study center because of acute decompensation of cirrhosis (ascites, overt encephalopathy, GI-hemorrhage, new onset of non-obstructive jaundice and/or bacterial infections), without ACLF (as defined according to the CANONIC study ) at hospitalization.

Description

Inclusion Criteria:

The patients admitted/referred to study center with AD of cirrhosis (ascites, overt encephalopathy, new onset of non-obstructive jaundice, GI-hemorrhage and/or bacterial infections), but without ACLF (as defined according to the CANONIC study) at study inclusion.

Exclusion Criteria:

1. Presence of ACLF at inclusion;
2. Pregnancy;
3. Age <18 years;
4. Patients with acute or subacute liver failure without underlying cirrhosis;
5. Patients with cirrhosis who develop decompensation in the postoperative period following partial hepatectomy;
6. Evidence of current malignancy except for non-melanocytic skin cancer and hepatocellular carcinoma within Milan criteria;
7. Presence or history of severe extra-hepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe heart disease (NYHA > II); severe chronic pulmonary disease (GOLD > III), severe neurological and psychiatric disorders);
8. HIV-positive patients
9. Previous liver or other transplantation
10. Admission/referral of more than 72 hours before inclusion
11. Patients who decline to participate or who cannot provide prior written informed consent and when there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent;
12. Physician´s denial (e.g. the investigator considers that the patient will not follow the protocol scheduled).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Group 1 patients with high risk of ACLF development (CLIF-C AD score ≥ 50)	Other: Observation protocol; The whole cohort will be followed for 3 months, while Group 1 will be followed more closely.
Group 2; Group 2 patients with low risk of ACLF (CLIF-C AD score <50)	Other: Observation protocol; The whole cohort will be followed for 3 months, while Group 1 will be followed more closely.
ACLF; ACLF-patients were specified the patients who were admitted at hospital with ACLF,	Other: Observation protocol; The whole cohort will be followed for 3 months, while Group 1 will be followed more closely.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients developing ACLF within 12 weeks and severity of ACLF development	Characterization of mechanisms responsible for ACLF development; Predictors of clinical course dynamics of ACLF evolution and mortality.; Identification and role of precipitating events for ACLF development.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score to PREDICT ACLF	-Calculate a Score to predict ACLF	12 weeks

Collaborators and Investigators

• Sponsor: Jonel Trebicka

Publications and helpful links

General Publications

• Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, Giovo I, Uschner FE, Jansen C, Jimenez C, Mookerjee R, Gustot T, Albillos A, Bañares R, Jarcuska P, Steib C, Reiberger T, Acevedo J, Gatti P, Shawcross DL, Zeuzem S, Zipprich A, Piano S, Berg T, Bruns T, Danielsen KV, Coenraad M, Merli M, Stauber R, Zoller H, Ramos JP, Solé C, Soriano G, de Gottardi A, Gronbaek H, Saliba F, Trautwein C, Kani HT, Francque S, Ryder S, Nahon P, Romero-Gomez M, Van Vlierberghe H, Francoz C, Manns M, Garcia-Lopez E, Tufoni M, Amoros A, Pavesi M, Sanchez C, Praktiknjo M, Curto A, Pitarch C, Putignano A, Moreno E, Bernal W, Aguilar F, Clària J, Ponzo P, Vitalis Z, Zaccherini G, Balogh B, Gerbes A, Vargas V, Alessandria C, Bernardi M, Ginès P, Moreau R, Angeli P, Jalan R, Arroyo V; PREDICT STUDY group of the EASL-CLIF CONSORTIUM. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. J Hepatol. 2021 May;74(5):1097-1108. doi: 10.1016/j.jhep.2020.11.019. Epub 2020 Nov 20.
• Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, Giovo I, Uschner FE, Jimenez C, Mookerjee R, Gustot T, Albillos A, Banares R, Janicko M, Steib C, Reiberger T, Acevedo J, Gatti P, Bernal W, Zeuzem S, Zipprich A, Piano S, Berg T, Bruns T, Bendtsen F, Coenraad M, Merli M, Stauber R, Zoller H, Ramos JP, Sole C, Soriano G, de Gottardi A, Gronbaek H, Saliba F, Trautwein C, Ozdogan OC, Francque S, Ryder S, Nahon P, Romero-Gomez M, Van Vlierberghe H, Francoz C, Manns M, Garcia E, Tufoni M, Amoros A, Pavesi M, Sanchez C, Curto A, Pitarch C, Putignano A, Moreno E, Shawcross D, Aguilar F, Claria J, Ponzo P, Jansen C, Vitalis Z, Zaccherini G, Balogh B, Vargas V, Montagnese S, Alessandria C, Bernardi M, Gines P, Jalan R, Moreau R, Angeli P, Arroyo V; PREDICT STUDY group of the EASL-CLIF Consortium. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J Hepatol. 2020 Oct;73(4):842-854. doi: 10.1016/j.jhep.2020.06.013. Epub 2020 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2017
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: February 13, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Pathologic Processes; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Fibrosis; Liver Failure; Acute-On-Chronic Liver Failure; Liver Cirrhosis
• Other Study ID Numbers: PREDICT (CardioDx)

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