Clinical trial NCT05056220: Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites
Official title: A Randomized Multicentre, Double-Blinded and Placebo-Controlled, Trial of Human Albumin in the Treatment of Decompensated Cirrhosis Guided by the MICROB-PREDICT Biomarker
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Decompensated Cirrhosis and Ascites
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: EASL - CLIF Consortium
First posted: 2021-09-24
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical biomarker validation trial is to test the effect of a predictive biomarker panel to human albumin infusions in patients with liver cirrhosis and ascites. The main questions it aims to answer are:

* If the predictive biomarker panel can identify patients who are likely to benefit from regular human albumin infusions
* If the predictive biomarker panel can lower the number-needed-to-treat of regular human albumin infusions in patients with liver cirrhosis and ascites

The predictive biomarker panel will stratify patients into either a high- or low-expected effect of human albumin infusions. Hereafter are participants randomized into treatment arms.

Participants in the active treatment arm will receive regular human albumin infusions during a course of 6 months. Infusions will occur every 10th day for the duration of the study.

Researchers will compare 20% human albumin infusions with regular 0.9% sodium chloride to identify the effects on the number of liver-related events.


Eligibility criteria: Inclusion Criteria:

* Decompensated liver cirrhosis defined as Child-Pugh score 7-12
* Clinical and/or ultrasound evidenced ascites
* Age ≥ 18 years
* At least five days since resolution of a decompensation event or any condition requiring hospitalisation

Exclusion Criteria:

* Patients with acute or subacute liver failure without underlying cirrhosis
* Patients with cirrhosis who develop decompensation in the postoperative period following partial hepatectomy
* Refractory ascites as defined by the International Ascites Club
* Existing TIPS
* Portal vein thrombosis
* Severe alcoholic hepatitis (Glasgow Alcoholic Hepatitis Score \> 11)
* Hepatic encephalopathy grade III-IV
* Current, planned or previous treatment with direct antiviral agents for hepatitis C virus (HCV) in the last six months Contraindications for human albumin infusion (pulmonary oedema, hypersensitivity etc.)
* Evidence of current malignancy except for non-melanocytic skin cancer and hepatocellular carcinoma within Barcelona Clinic Liver Cancer (BCLC)-0 or BCLC-A
* 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 Score ≥ C), severe neurological and psychiatric disorders, pulmonary arterial hypertension)
* HIV positive or other condition associated with and/or requiring immunosuppression
* Previous liver or other transplantation
* Pregnancy
* Breastfeeding
* Patients who decline to participate, patients who cannot provide prior written informed consent due to other causes than hepatic encephalopathy or patients with hepatic encephalopathy who cannot provide prior written informed consent and when there is documented evidence that the patient has no legal surrogate decision maker or sufficient ability to provide delayed informed consent
* Physician's denial (investigator considers that the patient will not adhere to the study protocol scheduled, e.g. in case of heavy drinking)
* Participation in another study within 3 months prior to screening

Primary outcomes:
measure: Cumulative number of liver-related clinical outcomes
timeFrame: 6 months
Secondary outcomes:
measure: 6-months survival
timeFrame: 6 months
measure: The number of episodes of acute-on-chronic liver failures
timeFrame: 6 months
measure: Number of organ failures
timeFrame: 6 months
measure: Time-to-first liver-related clinical outcome
timeFrame: 6 months
measure: Change in SF-36
timeFrame: 6 months
measure: Change in CLDQ
timeFrame: 6 months
measure: Change in EQ-5D-5L
timeFrame: 6 months
measure: Time to first hospital admission (in days)
timeFrame: 180 days
measure: Number of hospital admissions
timeFrame: 180 days
measure: Days spent on hospitalization (in days)
timeFrame: 180 days
measure: Number of intensive care unit admissions
timeFrame: 180 days
measure: Length of intensive care unit admissions (in days)
timeFrame: 180 days
measure: Number of large volume paracentesis
timeFrame: 6 months
measure: Analysis of the cost/effectiveness ratio
timeFrame: 6 months
measure: Health economic evaluation
timeFrame: 6 months
measure: Changes in serum albumin levels
timeFrame: 6 months
measure: Number of treatment-related adverse events
timeFrame: 6 months
measure: Number of treatment-related serious adverse events
timeFrame: 6 months
measure: Signatures associated with a poor prognosis as defined by the Microb-Predict biomarker
timeFrame: 6 months
measure: Incidence of refractory ascites
timeFrame: 6 months
measure: Incidence of variceal bleeding
timeFrame: 6 months
measure: Incidence of spontaneous bacterial peritonitis
timeFrame: 6 months
measure: Incidence of infection requiring hospitalization
timeFrame: 6 months
measure: Incidence of acute kidney injury >= 1B
timeFrame: 6 months
measure: Incidence of hepatorenal syndrome acute kidney injury
timeFrame: 6 months
measure: Incidence of overt hepatic encephalopathy
timeFrame: 6 months
measure: Incidence of liver transplantation
timeFrame: 6 months
measure: Incidence of TIPS insertion
timeFrame: 6 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Katholieke Universiteit Leuven
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Leiden
country: Netherlands
facility: Academisch Ziekenhuis Leiden
city: Leiderdorp
country: Netherlands
facility: Alrijne Ziekenhuis Leiden
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: Odense University Hospital
name: Aleksander Krag, Professor
role: PRINCIPAL_INVESTIGATOR
References: