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

Liver Cirrhosis With Acute Decompensation Clinical Trial

— PREDICT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03056612
• Other study ID #: PREDICT
• Status: Completed
• Start date: March 31, 2017
• Est. completion date: October 31, 2018

Study information

• Verified date: April 2019
• Source: European Foundation for Study of Chronic Liver Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1314
• Est. completion date: October 31, 2018
• Est. primary completion date: July 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Fibrosis
• Hepatic Insufficiency
• Liver Cirrhosis
• Liver Cirrhosis With Acute Decompensation
• Liver Failure

Intervention

Other:
• Observation protocol
The whole cohort will be followed for 3 months, while Group 1 will be followed more closely.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Jonel Trebicka

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  France,  Germany,  Hungary,  Italy,  Netherlands,  Portugal,  Slovakia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Score to PREDICT ACLF	-Calculate a Score to predict ACLF	12 weeks