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

Decompensated Cirrhosis and Ascites Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05056220
• Other study ID #: 2022-501006-34-01
• Secondary ID: 825694
• Status: Recruiting
• Phase: Phase 3
• Start date: February 26, 2024
• Est. completion date: April 2025

Study information

• Verified date: April 2024
• Source: Odense University Hospital
• Contact: Aleksander Krag, Professor
• Phone: +4566113333
• Email: albtrial[@]rsyd.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: April 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ascites
• Decompensated Cirrhosis and Ascites
• Fibrosis
• Liver Cirrhosis

Intervention

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)
• 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)

Locations

Country	Name	City	State
Belgium	Katholieke Universiteit Leuven	Leuven
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Münster	Münster
Hungary	Debreceni Egyetem	Debrecen
Netherlands	Academisch Ziekenhuis Leiden	Leiden
Netherlands	Alrijne Ziekenhuis Leiden	Leiderdorp
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Del Mar	Barcelona
United Kingdom	King's College Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Aleksander Krag	EASL - CLIF Consortium

Countries where clinical trial is conducted

Belgium,  Denmark,  Germany,  Hungary,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative number of liver-related clinical outcomes	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.	6 months
Secondary	6-months survival		6 months
Secondary	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
Secondary	Number of organ failures	Where an organ failure is defined according to the CLIF-C ACLF definition.	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to first hospital admission (in days)		180 days
Secondary	Number of hospital admissions		180 days
Secondary	Days spent on hospitalization (in days)		180 days
Secondary	Number of intensive care unit admissions		180 days
Secondary	Length of intensive care unit admissions (in days)		180 days
Secondary	Number of large volume paracentesis		6 months
Secondary	Analysis of the cost/effectiveness ratio	Analyzed by an incremental cost-effectiveness ratio (ICER) calculation	6 months
Secondary	Health economic evaluation	Analyzed by the change in quality-adjusted life years (QALYs) relative to the ICER.	6 months
Secondary	Changes in serum albumin levels	Measured from baseline and throughout the trial in grams per litre (g/L)	6 months
Secondary	Number of treatment-related adverse events	Adverse events which are deemed related to the trial intervention	6 months
Secondary	Number of treatment-related serious adverse events	Adverse events which are deemed related to the trial intervention	6 months
Secondary	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
Secondary	Incidence of refractory ascites		6 months
Secondary	Incidence of variceal bleeding		6 months
Secondary	Incidence of spontaneous bacterial peritonitis		6 months
Secondary	Incidence of infection requiring hospitalization		6 months
Secondary	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
Secondary	Incidence of hepatorenal syndrome acute kidney injury		6 months
Secondary	Incidence of overt hepatic encephalopathy		6 months
Secondary	Incidence of liver transplantation		6 months
Secondary	Incidence of TIPS insertion		6 months