Effects of Long-Term Administration of Human Albumin in Subjects With Decompensated Cirrhosis and Ascites

Study Overview
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Brief Summary
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This is a phase 3, multicenter, randomized, controlled, parallel-group, and open-label clinical study to evaluate the efficacy of standard medical treatment (SMT) + Albutein 20% administration versus SMT alone in subjects with decompensated cirrhosis and ascites. The study population will consist of subjects being discharged after hospitalization for acute decompensation of liver cirrhosis with ascites (or with prior history of ascites requiring diuretic therapy) with or without acute-on-chronic liver failure (ACLF) at admission or during hospitalization but without ACLF at discharge.

Official Title
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Prevention of Mortality With Long-Term Administration of Human Albumin in Subjects With Decompensated Cirrhosis and Ascites

Conditions
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Decompensated Cirrhosis and Ascites

Intervention / Treatment
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* Drug: Albutein 20% Injectable Solution
* Other: Standard medical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject ≥18 years of age. Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology). Subjects who have been hospitalized for acute decompensation of liver cirrhosis with ascites (or with prior history of ascites requiring diuretic therapy) with or without ACLF at admission or during hospitalization but without ACLF at Screening. In subjects with cirrhosis due to hepatitis B virus, decompensation must occur in the setting of continuous (no less than 3 months) appropriate antiviral therapy. In subjects with cirrhosis due to hepatitis C virus, only decompensated patients who will not receive antiviral therapy during the study period will be included (Subjects receiving antiviral therapy within 14 days prior to enrollment cannot be included in the study). In subjects with cirrhosis due to autoimmune hepatitis, decompensation must occur in the setting of continuous immunosuppressive therapy. Subjects must be willing and able to provide written informed consent or have an authorized representative able to provide written informed consent on behalf of the subject in accordance with local law and institutional policy. CLIF-C AD score > 50 points at screening. Exclusion Criteria: Subjects with ACLF at Screening Subjects with type 1 HRS currently on treatment with vasoconstrictors or hemodialysis. Subjects with TIPS or other surgical porto-caval shunts. Subjects with refractory ascites as defined by ICA criteria without any other event of acute decompensation. Subjects receiving dual anti-platelet therapy or anti-coagulant therapy (exception: DVT prophylaxis). Subjects with ongoing endoscopic eradication of esophageal varices with ≤ 2 endoscopic sessions completed before screening. Subjects with evidence of current locally advanced or metastatic malignancy. Subjects with acute or chronic heart failure (New York Heart Association [NYHA]). Subjects with severe (grade III or IV) pulmonary disease (Global Obstructive Lung Disease [GOLD]). Subjects with nephropathy with renal failure with serum creatinine >2 mg/dL or systemic hypertension. Subjects with severe psychiatric disorders. Subjects with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection. Females who are pregnant, breastfeeding, or if of childbearing potential, unwilling to practice effective methods of contraception Subjects with previous liver transplantation. Subjects with known or suspected hypersensitivity to albumin. Subjects participating in another clinical study within 3 months prior to screening. Subjects with active drug addiction (exceptions: active alcoholism or marijuana). In the opinion of the investigator, the subject may have compliance problems with the protocol and the procedures of the protocol. Subjects with ongoing or recent variceal bleeding (subjects can be included 2 weeks after hemorrhagic episode). Subjects with septic shock at screening. Subjects with ongoing SBP infection (subjects can be included upon resolution). Subjects with current infection of COVID19, those who are less than 14 days post recovery, or those who have clinical signs and symptoms consistent with COVID19 infection.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Medical Treatment + Albutein 20%<br>Standard Medical Treatment plus Albutein 20% administrations | Drug: Albutein 20% Injectable Solution<br>* Within 96 hours after discharge and following randomization, subjects will receive the first Albutein 20% infusion at the dose of 1.5 g/kg body weight (maximum 100 grams per subject). Thereafter, subjects will receive Albutein 20% infusions at the dose of 1.5 g/kg body weight (maximum 100 grams per subject) every 10 ± 2 days for the rest of the study (up to a maximum of 12 months). Subjects in this treatment group will also receive SMT.<br>Other: Standard medical treatment<br>* Subjects will receive SMT according to published guidelines for the management of decompensated cirrhosis.<br>|
| Active Comparator: Standard Medical Treatment<br>The sites will follow the Standard Medical Treatment as per their Standard of Care. | Other: Standard medical treatment<br>* Subjects will receive SMT according to published guidelines for the management of decompensated cirrhosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to liver transplantation or death (whichever comes first) through 1 year after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to liver transplantation or death (whichever comes first) through 3 months after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 3 months | 
| Time to liver transplantation or death (whichever comes first) through 6 months after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 6 months | 
| Time to death through 3 months after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 3 months | 
| Time to death through 6 months after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 6 months | 
| Time to death through 1 year after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 12 months | 
| Total number of paracenteses through 1 year after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 12 months | 
| Total number of incidences of refractory ascites according to the International Club of Ascites (ICA) through 1 year after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone |  | 12 months |