Clinical trial NCT06855056: Validation of New Prognostic Biomarkers in Patients With Decompensated Cirrhosis
Official title: Validation of New Prognostic biomarkerRs in Patients With cirrhOsis diScharged After a hosPitalization Due to acutE deCompensation or acuTe-on-chronic Liver Failure
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Liver Cirrhosis
Decompensated Cirrhosis of Liver
Keywords: Decompensated Liver Cirrhosis
Acute on Chronic Liver Failure (ACLF)
Liver Diseases
Liver Cirrhosis
Biomarkers
Lead sponsor: European Foundation for Study of Chronic Liver Failure
Sponsor class: OTHER
Collaborators: name: Universität Münster
name: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Hospital Universitari Vall d'Hebron Research Institute
name: Hospital Clinic de Barcelona, Barcelona, Spain
name: Hospital Universitario Ramon y Cajal
name: Beaujon Hospital
name: University Hospital, Aachen
name: A.O.U. Città della Salute e della Scienza
First posted: 2025-03-03
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients eligible for this study will be patients with decompensated cirrhosis expected to be discharged from the hospital within 48 hours after an index admission for AD according to the EASL-CLIF criteria.

Brief summary: The study aims to test the effectiveness of new biomarkers (measurable molecules in our body) in predicting the health outcome of patients with liver cirrhosis discharged from the hospital after a serious complication of the disease

Detailed description: The PROSPECT study is part of the larger EU H2020 DECISION project, which aims to analyze and clarify the pathophysiological mechanisms of decompensated cirrhosis at the systemic level and its transition to ACLF, with the goal of significantly reducing mortality through therapies tailored to the specific needs of individual patients or patient groups.

As planned in the DECISION project, the biological samples of three large cohorts of patients with cirrhosis admitted to hospital for acute decompensation (AD) without ACLF, deriving from the EF-CLIF-promoted observational studies CANONIC and PREDICT (Europe) and ACLARA (South America) were analyzed to measure lipidomics, epigenomics, whole-blood transcriptomics, micro-RNA, serum metabolomics, plasma cytokines, and plasma extracellular vesicles.

Both system medicine approaches and more traditional methods of analysis have been applied to analyze and interpret the results. The analyses are still ongoing due to the very high number of variables and the complexity of associating -omics to clinical data, yet, some of these analyses have already generated solid data allowing the identification of novel biomarkers which can be further tested.

In the PROSPECT study, patients hospitalized for acute decompensation of liver cirrhosis, who meet the inclusion and exclusion criteria, will be enrolled after providing signed informed consent. Participants will be screened and included in the study within 48 hours prior to the expected discharge from the hospital. The study will last 180 days and will include an initial visit during which clinical parameters and additional blood samples will be collected, followed by two follow-up visits - which can also be conducted by phone - during which only clinical information will be gathered. Samples will be analyzed to determine the biomarkers selected within the DECISION project and parameters related to the following pathophysiological mechanisms:

* systemic inflammation
* blood and microRNA transcriptome
* the metabolomic landscape
* albumin structure and function
* coagulation assays
* extracellular vesicles
* endothelial function

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 80 years.
2. Patients with decompensated cirrhosis admitted to hospital due to AD according to the EASL-CLIF criteria (rapid onset of ascites, hepatic encephalopathy, portal hypertensive- related gastrointestinal bleeding, bacterial infection, or any combination of these), including those who presented ACLF during hospitalization.
3. Recovery from AD and expected to be discharged within the next 48 hours.

Exclusion Criteria:

1. Admission for planned diagnostic or therapeutic procedures
2. Active malignancy (except for hepatocellular carcinoma within the Milan criteria or nonmelanocytic skin cancer)
3. Antiviral treatment for hepatitis C, B and delta initiated in the last 6 months or planned to be initiated in the following 6 months.
4. HIV positive (except undergoing treatment and who do not exhibit clinical manifestations of AIDS).
5. Ongoing alcohol use disorder with an expected low adherence to prescriptions as judged by physician
6. Previous liver or other organ transplantation
7. Patients with TIPS or other surgical porto-caval shunts
8. Chronic organic renal failure stage IV and V or estimated Glomerular Filtration Rate \<20 ml/min according to the MDRD equations
9. Chronic heart failure NYHA class III or IV
10. Pulmonary disease GOLD III or IV
11. Patients with a history of significant extrahepatic disease with life expectancy \<6 months
12. Severe psychiatric disorders
13. Pregnancy and breast-feeding
14. Expected low adherence to study protocol as judged by physician
15. Patients who cannot provide written informed consent or refuse to participate

Primary outcomes:
measure: To test the prognostic accuracy of novel biomarkers identified within the DECISION project.
timeFrame: Until September 30th 2025
Secondary outcomes:
measure: To characterize the clinical and biological features at the time of discharge predicting the 6-month outcome and the different trajectories of patients surviving a hospitalization for AD complicated or not by ACLF.
timeFrame: Until September 30th 2025
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hospital Beaujon
city: Aachen
country: Germany
facility: University Hospital, Aachen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di S.Orsola
state: Italia
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron Research Institute
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References: