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

Phase 3RecruitingNCT05056220

Aleksander Krag240 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

240

Conditions

Decompensated Cirrhosis and Ascites

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

Katholieke Universiteit Leuven

Leuven, Belgium

RECRUITING

Herlev Hospital

Herlev, Denmark

RECRUITING

Odense University Hospital

Odense, Denmark

RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, Germany

RECRUITING

Universitätsklinikum Jena

Jena, Germany

RECRUITING

Universitätsklinikum Münster

Münster, Germany

RECRUITING

Debreceni Egyetem

Debrecen, Hungary

RECRUITING

Academisch Ziekenhuis Leiden

Leiden, Netherlands

RECRUITING

Alrijne Ziekenhuis Leiden

Leiderdorp, Netherlands

RECRUITING

Hospital Clinic Barcelona

Barcelona, Spain

RECRUITING

...and 2 more locations

Outcomes

Primary Outcomes

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

Time frame: 6 months

Secondary Outcomes

6-months survival

Time frame: 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.

Time frame: 6 months

Number of organ failures

Where an organ failure is defined according to the CLIF-C ACLF definition.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 6 months

Time to first hospital admission (in days)

Time frame: 180 days

Number of hospital admissions

Time frame: 180 days

Days spent on hospitalization (in days)

Time frame: 180 days

Number of intensive care unit admissions

Time frame: 180 days

Length of intensive care unit admissions (in days)

Time frame: 180 days

Number of large volume paracentesis

Time frame: 6 months

Analysis of the cost/effectiveness ratio

Analyzed by an incremental cost-effectiveness ratio (ICER) calculation

Time frame: 6 months

Health economic evaluation

Analyzed by the change in quality-adjusted life years (QALYs) relative to the ICER.

Time frame: 6 months

Changes in serum albumin levels

Measured from baseline and throughout the trial in grams per litre (g/L)

Time frame: 6 months

Number of treatment-related adverse events

Adverse events which are deemed related to the trial intervention

Time frame: 6 months

Number of treatment-related serious adverse events

Adverse events which are deemed related to the trial intervention

Time frame: 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)

Time frame: 6 months

Incidence of refractory ascites

Time frame: 6 months

Incidence of variceal bleeding

Time frame: 6 months

Incidence of spontaneous bacterial peritonitis

Time frame: 6 months

Incidence of infection requiring hospitalization

Time frame: 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.

Time frame: 6 months

Incidence of hepatorenal syndrome acute kidney injury

Time frame: 6 months

Incidence of overt hepatic encephalopathy

Time frame: 6 months

Incidence of liver transplantation

Time frame: 6 months

Incidence of TIPS insertion or revision

Time frame: 6 months

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

Overview

Conditions

Interventions

Eligibility

Locations (12)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts