Tuesday, October 17, 2017

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

on behalf of the EASL-CLIF Consortium

International-European, investigator-initiated, multicenter, prospective, observational study

Performed in centers that belong to

the European Foundation for the Study of Chronic Liver failure (EF-CLIF foundation)-EASL-CLIF Consortium

About Predict Study

Background

The CANONIC Study consisted in a 28-day detailed prospective observational investigation in patients admitted to hospital for the treatment of an acute decompensation of cirrhosis. The main aim of the CANONIC study was to characterize acute-on-chronic liver failure (ACLF) regarding diagnostic criteria, stages and natural history up to one year of follow up.  Three quarters of the ACLF-patients (in total ca. 400) recruited in the CANONIC study presented with ACLF at enrolment. Therefore, the critical period prior to ACLF development and possible predictors could not be sufficiently analyzed in these patients due to the study aim and design. Moreover, the limited knowledge about the ACLF syndrome itself rendered the prospective and detailed analysis of predictors for the development of ACLF impossible.

The PREDICT Study is therefore designed to prospectively observe patients with Acute Decompensation (AD) at risk of developing ACLF within three months and to discover clinical, laboratory and patho-physiological (using prospective ancillary studies) predictors and mechanisms involved in the development and clinical course of ACLF, which might help to prevent and treat ACLF. 

AIMS

The aim of this study is to assess prospectively the critical period prior to the development of 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).

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.

Study type, population and design

  • 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 foundation)-EASL-CLIF Consortium.
  • 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.
  •  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 ≥ 60) and in Group 2 patients with low risk of ACLF (CLIF-C AD score <60). 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.
  • Prospective collection of biological material and performance of ancillary studies investigating predictors for development and pathogenesis of ACLF.

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