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

Study Overview
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Brief Summary
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ALB-TRIAL

Detailed Description
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Albumin Trial (ALB-TRIAL)

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

Conditions
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Decompensated Cirrhosis and Ascites

Intervention / Treatment
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* Drug: Human albumin
* Drug: sodium chloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High expected effect: Human Albumin 20% + Standard Medical Treatment<br> | Drug: Human albumin<br>* 20%<br>|
| Placebo Comparator: High expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment<br> | Drug: sodium chloride<br>* 0.9%<br>|
| Active Comparator: Low expected effect: Human Albumin 20% + Standard Medical Treatment<br> | Drug: Human albumin<br>* 20%<br>|
| Placebo Comparator: Low expected effect: Saline (NaCl 0.9%) + Standard Medical Treatment<br> | Drug: sodium chloride<br>* 0.9%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 |  | 6 months |