Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites
- Conditions
- Decompensated Cirrhosis and Ascites
- Interventions
- Registration Number
- NCT05056220
- Lead Sponsor
- Aleksander Krag
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment sodium chloride Participants stratified to a high expected effect of human albumin and randomized to placebo treatment with 0.9% NaCl (saline) infusions. High expected effect: Human Albumin 20% + Standard Medical Treatment Human albumin Participants stratified to a high expected effect of human albumin and randomized to active treatment with 20% Human Albumin infusions. Low expected effect: Human Albumin 20% + Standard Medical Treatment Human albumin Participants stratified to a low expected effect of human albumin and randomized to active treatment with 20% Human Albumin infusions. Low expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment sodium chloride Participants stratified to a low expected effect of human albumin and randomized to placebo treatment with 0.9% NaCl (saline) infusions.
- Primary Outcome Measures
Name Time Method Cumulative number of liver-related clinical outcomes 6 months 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.
- Secondary Outcome Measures
Name Time Method The number of episodes of acute-on-chronic liver failures 6 months Acute-on-chronic liver failure (ACLF) is defined according to the CLIF-C ACLF definition.
Time to first hospital admission (in days) 180 days Number of intensive care unit admissions 180 days Number of large volume paracentesis 6 months Health economic evaluation 6 months Analyzed by the change in quality-adjusted life years (QALYs) relative to the ICER.
Number of treatment-related adverse events 6 months Adverse events which are deemed related to the trial intervention
Time-to-first liver-related clinical outcome 6 months 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 survival 6 months Number of organ failures 6 months Where an organ failure is defined according to the CLIF-C ACLF definition.
Change in CLDQ 6 months 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).
Change in EQ-5D-5L 6 months 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.
Number of hospital admissions 180 days Analysis of the cost/effectiveness ratio 6 months Analyzed by an incremental cost-effectiveness ratio (ICER) calculation
Signatures associated with a poor prognosis as defined by the Microb-Predict biomarker 6 months Change in concentration of the panel of predictive circulating metabolites compared to metabolite levels in other body fluid compartments (blood, urin, stool and saliva)
Incidence of variceal bleeding 6 months Incidence of hepatorenal syndrome acute kidney injury 6 months Incidence of overt hepatic encephalopathy 6 months Incidence of TIPS insertion 6 months Changes in serum albumin levels 6 months Measured from baseline and throughout the trial in grams per litre (g/L)
Number of treatment-related serious adverse events 6 months Adverse events which are deemed related to the trial intervention
Incidence of refractory ascites 6 months Incidence of spontaneous bacterial peritonitis 6 months Incidence of infection requiring hospitalization 6 months Incidence of acute kidney injury >= 1B 6 months According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition ranging from stage 1A to 3 where a higher stage is worse.
Incidence of liver transplantation 6 months Change in SF-36 6 months 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.
Days spent on hospitalization (in days) 180 days Length of intensive care unit admissions (in days) 180 days
Trial Locations
- Locations (12)
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Academisch Ziekenhuis Leiden
🇳🇱Leiden, Netherlands
Alrijne Ziekenhuis Leiden
🇳🇱Leiderdorp, Netherlands
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Del Mar
🇪🇸Barcelona, Spain
King's College Hospital
🇬🇧London, United Kingdom
Katholieke Universiteit Leuven
🇧🇪Leuven, Belgium
Herlev Hospital
🇩🇰Herlev, Denmark
Odense University Hospital
🇩🇰Odense, Denmark
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany