Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites

A Randomized Multicentre, Double-Blinded and Placebo-Controlled, Trial of Human Albumin in the Treatment of Decompensated Cirrhosis Guided by the MICROB-PREDICT Biomarker

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.

Study Overview

• Status: Recruiting
• Conditions: Decompensated Cirrhosis and Ascites
• Intervention / Treatment: Drug: Human albumin; Drug: sodium chloride

Detailed Description

Albumin Trial (ALB-TRIAL)

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Aleksander Krag, Professor; Phone Number: +4566113333; Email: albtrial@rsyd.dk
• Study Contact Backup: Name: Jonel Trebicka, Professor

Study Locations

• Belgium
  • Leuven, Belgium
    • Recruiting
    • Katholieke Universiteit Leuven
    • Contact: Wim Laleman
• Denmark
  • Herlev, Denmark
    • Recruiting
    • Herlev Hospital
    • Contact: Mette Lehmann Andersen
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Nikolaj Torp
• Germany
  • Berlin, Germany
    • Recruiting
    • Charité - Universitätsmedizin Berlin
    • Contact: Cornelius Engelmann
  • Jena, Germany
    • Recruiting
    • Universitatsklinikum Jena
    • Contact: Alexander Zipprich
  • Münster, Germany
    • Recruiting
    • Universitatsklinikum Munster
    • Contact: Jonel Trebicka
• Hungary
  • Debrecen, Hungary
    • Recruiting
    • Debreceni Egyetem
    • Contact: Maria Papp
• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • Academisch Ziekenhuis Leiden
    • Contact: Minneke Coenraad
  • Leiderdorp, Netherlands
    • Recruiting
    • Alrijne Ziekenhuis Leiden
    • Contact: Sunje Abraham
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
    • Contact: Montserrat Garcia Retortillo
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic Barcelona
    • Contact: Pere Ginés
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • King's College Hospital
    • Contact: Debbie Shawcross

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 inserted <6 months ago
• Portal vein thrombosis without signs of cavernous transformation or recanalization
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High expected effect: Human Albumin 20% + Standard Medical Treatment; Participants stratified to a high expected effect of human albumin and randomized to active treatment with 20% Human Albumin infusions.	Drug: Human albumin; 20% Human Albumin infusions (every 10th day +/- 4 days) with dosing according to the participants bodyweight (1.5 grams of albumin per kg bodyweight with a maximum of 100 grams)
Placebo Comparator: High expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment; Participants stratified to a high expected effect of human albumin and randomized to placebo treatment with 0.9% NaCl (saline) infusions.	Drug: sodium chloride; 0.9% NaCl infusions (every 10th day +/- 4 days) with dosing according to the corresponding volume used of 20% Human Albumin (1.5 grams of albumin per kg bodyweight with a maximum of 100 grams)
Active Comparator: Low expected effect: Human Albumin 20% + Standard Medical Treatment; Participants stratified to a low expected effect of human albumin and randomized to active treatment with 20% Human Albumin infusions.	Drug: Human albumin; 20% Human Albumin infusions (every 10th day +/- 4 days) with dosing according to the participants bodyweight (1.5 grams of albumin per kg bodyweight with a maximum of 100 grams)
Placebo Comparator: Low expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment; Participants stratified to a low expected effect of human albumin and randomized to placebo treatment with 0.9% NaCl (saline) infusions.	Drug: sodium chloride; 0.9% NaCl infusions (every 10th day +/- 4 days) with dosing according to the corresponding volume used of 20% Human Albumin (1.5 grams of albumin per kg bodyweight with a maximum of 100 grams)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative number of liver-related clinical outcomes	Cumulative number of liver-related clinical outcomes (variceal bleeding, ascites, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury and overt hepatic encephalopathy) and TIPS (insertion or revision) with death and liver transplantation as counting and censoring events	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-months survival		6 months
The number of episodes of acute-on-chronic liver failures	Acute-on-chronic liver failure (ACLF) is defined according to the CLIF-C ACLF definition.	6 months
Number of organ failures	Where an organ failure is defined according to the CLIF-C ACLF definition.	6 months
Time-to-first liver-related clinical outcome	A liver-related clinical outcome is defined as variceal bleeding, ascites, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury (>=1B), overt hepatic encephalopathy, TIPS insertion, liver transplantation or death. Time to any of these outcomes are defined as the time from trial inclusion until 1) the date of diagnosis of any of the complications, 2) the date of the procedure (TIPS or liver transplantation) or date of death.	6 months
Change in SF-36	Quality of life for participants, as measured by Short Form 36 (SF-36), ranging from 0 to 100 with a score of 0 equal to maximum disability and score of 100 no disability.	6 months
Change in CLDQ	Quality of life for participants, as measured by the Chronic Liver Disease Questionnaire (CLDQ), consisting of 29 items within 7 domains. Response on a Likert scale ranging from 1 (most impairment) to 7 (least impairment). Total score by adding score for each item and divide by number of items (29).	6 months
Change in EQ-5D-5L	Quality of life for participants, as measured by the EuroQoL-5 Domain, 5 levels (EQ-5D-5L). Consist of 5 domains with 5 levels where the lowest level (1) is the worst imaginable health and highest level (5) is the best imaginable health.	6 months
Time to first hospital admission (in days)		180 days
Number of hospital admissions		180 days
Days spent on hospitalization (in days)		180 days
Number of intensive care unit admissions		180 days
Length of intensive care unit admissions (in days)		180 days
Number of large volume paracentesis		6 months
Analysis of the cost/effectiveness ratio	Analyzed by an incremental cost-effectiveness ratio (ICER) calculation	6 months
Health economic evaluation	Analyzed by the change in quality-adjusted life years (QALYs) relative to the ICER.	6 months
Changes in serum albumin levels	Measured from baseline and throughout the trial in grams per litre (g/L)	6 months
Number of treatment-related adverse events	Adverse events which are deemed related to the trial intervention	6 months
Number of treatment-related serious adverse events	Adverse events which are deemed related to the trial intervention	6 months
Signatures associated with a poor prognosis as defined by the Microb-Predict biomarker	Change in concentration of the panel of predictive circulating metabolites compared to metabolite levels in other body fluid compartments (blood, urin, stool and saliva)	6 months
Incidence of refractory ascites		6 months
Incidence of variceal bleeding		6 months
Incidence of spontaneous bacterial peritonitis		6 months
Incidence of infection requiring hospitalization		6 months
Incidence of acute kidney injury >= 1B	According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition ranging from stage 1A to 3 where a higher stage is worse.	6 months
Incidence of hepatorenal syndrome acute kidney injury		6 months
Incidence of overt hepatic encephalopathy		6 months
Incidence of liver transplantation		6 months
Incidence of TIPS insertion or revision		6 months

Collaborators and Investigators

• Sponsor: Aleksander Krag
• Collaborators: EASL - CLIF Consortium
• Investigators: Principal Investigator: Aleksander Krag, Professor, Odense University Hospital

Publications and helpful links

General Publications

• Torp N, Israelsen M, Coenraad M, Papp M, Shawcross D, Korenjak M, Angeli P, Laleman W, Juanola A, Gines P, Trebicka J, Krag A; MICROB-PREDICT Consortium. Personalised human albumin in patients with cirrhosis and ascites: design and rationale for the ALB-TRIAL - a randomised clinical biomarker validation trial. BMJ Open. 2024 Feb 14;14(2):e079309. doi: 10.1136/bmjopen-2023-079309.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 24, 2021

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ascites; Amino Acids, Peptides, and Proteins; Proteins; Blood Proteins; Inorganic Chemicals; Chlorine Compounds; Albumins; Sodium Compounds; Chlorides; Hydrochloric Acid; Serum Albumin; Sodium Chloride; Serum Albumin, Human
• Other Study ID Numbers: 2022-501006-34-01; 825694 (Other Grant/Funding Number: HORIZON 2020)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No