Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03056612
Recruitment Status : Completed
First Posted : February 17, 2017
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Jonel Trebicka, European Foundation for Study of Chronic Liver Failure

Tracking Information
First Submitted Date February 13, 2017
First Posted Date February 17, 2017
Last Update Posted Date April 12, 2019
Actual Study Start Date March 31, 2017
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 14, 2017)
Number of patients developing ACLF within 12 weeks and severity of ACLF development [ Time Frame: 12 weeks ]
  • 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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: March 2, 2017)
Score to PREDICT ACLF [ Time Frame: 12 weeks ]
-Calculate a Score to predict ACLF
Original Secondary Outcome Measures
 (submitted: February 14, 2017)
Score to PREDICT ACLF [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Predicting Acute-on-Chronic Liver Failure in Cirrhosis (PREDICT) Study
Official Title Predicting Acute-on-Chronic Liver Failure in Cirrhosis (PREDICT) Study
Brief 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).
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
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
peripheral serum, plasma, PBMC/PMN, urine, hair (in case of alcohol abuse), ascites (if any), stool, saliva
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.
Condition Liver Cirrhosis With Acute Decompensation
Intervention Other: Observation protocol
The whole cohort will be followed for 3 months, while Group 1 will be followed more closely.
Study Groups/Cohorts
  • Group 1
    Group 1 patients with high risk of ACLF development (CLIF-C AD score ≥ 50)
    Intervention: Other: Observation protocol
  • Group 2
    Group 2 patients with low risk of ACLF (CLIF-C AD score <50)
    Intervention: Other: Observation protocol
  • ACLF
    ACLF-patients were specified the patients who were admitted at hospital with ACLF,
    Intervention: Other: Observation protocol
Publications * Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, Giovo I, Uschner FE, Jimenez C, Mookerjee R, Gustot T, Albillos A, Bañares 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, Solè C, Soriano G, de Gottardi A, Gronbaek H, Saliba F, Trautwein C, Özdogan 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, Clària J, Ponzo P, Jansen C, Vitalis Z, Zaccherini G, Balogh B, Vargas V, Montagnese S, Alessandria C, Bernardi M, Ginès 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: April 10, 2019)
1314
Original Estimated Enrollment
 (submitted: February 14, 2017)
1200
Actual Study Completion Date October 31, 2018
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

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).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Austria,   Belgium,   Denmark,   France,   Germany,   Hungary,   Italy,   Netherlands,   Portugal,   Slovakia,   Spain,   Switzerland,   Turkey,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03056612
Other Study ID Numbers PREDICT
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Jonel Trebicka, European Foundation for Study of Chronic Liver Failure
Study Sponsor Jonel Trebicka
Collaborators Not Provided
Investigators Not Provided
PRS Account European Foundation for Study of Chronic Liver Failure
Verification Date April 2019