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

NCT ID: NCT03451292

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-24
• Study Completion Date: 2024-05-21

Brief Summary

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 participants with decompensated cirrhosis and ascites. The study population will consist of participants 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.

Conditions

Decompensated Cirrhosis and Ascites

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SMT + Albutein 20%

Participants received Albutein 20%, at a dose of 1.5 grams/kilograms (g/kg), based on their body weight (maximum 100 grams per participant), as an intravenous (IV) infusion on Day 1, followed by the same dose of Albutein 20% every 10±2 days along with standard medical treatment (SMT) administered as per institution standards for the management of decompensated cirrhosis up to 12 months.

Group Type: EXPERIMENTAL

Albutein 20%

Intervention Type: DRUG

Injectable solution

SMT

Intervention Type: OTHER

Participants received SMT according to institution standards for the management of decompensated cirrhosis.

SMT

Participants received SMT up to 12 months as per institution standards for the management of decompensated cirrhosis.

Group Type: ACTIVE_COMPARATOR

SMT

Intervention Type: OTHER

Participants received SMT according to institution standards for the management of decompensated cirrhosis.

Interventions

Albutein 20%

Injectable solution

Intervention Type: DRUG

SMT

Participants received SMT according to institution standards for the management of decompensated cirrhosis.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Male or female participants ≥18 years of age.
• Participants with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology).
• Participants 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 participants with cirrhosis due to hepatitis B virus, decompensation must occur in the setting of continuous (no less than 3 months) appropriate antiviral therapy.
• In participants with cirrhosis due to hepatitis C virus, only decompensated participants who will not receive antiviral therapy during the study period will be included (Participants receiving antiviral therapy within 14 days prior to enrollment cannot be included in the study).
• In participants with cirrhosis due to autoimmune hepatitis, decompensation must occur in the setting of continuous immunosuppressive therapy.
• Participants 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 participant in accordance with local law and institutional policy.
• Chronic liver failure-consortium acute decompensation (CLIF-C AD) score > 50 points at screening.

Exclusion Criteria

• Participants with ACLF at Screening
• Participants with type 1 hepatorenal syndrome (HRS) currently on treatment with vasoconstrictors or hemodialysis.
• Participants with transjugular intrahepatic portosystemic shunt (TIPS) or other surgical porto-caval shunts.
• Participants with refractory ascites as defined by the International Club of Ascites (ICA) criteria without any other event of acute decompensation.
• Participants receiving dual anti-platelet therapy or anti-coagulant therapy (exception: deep vein thrombosis (DVT) prophylaxis).
• Participants with ongoing endoscopic eradication of esophageal varices with ≤ 2 endoscopic sessions completed before screening.
• Participants with evidence of current locally advanced or metastatic malignancy.
• Participants with acute or chronic heart failure (New York Heart Association [NYHA]).
• Participants with severe (grade III or IV) pulmonary disease (Global Obstructive Lung Disease [GOLD]).
• Participants with nephropathy with renal failure with serum creatinine >2 milligrams/deciliters (mg/dL) or systemic hypertension.
• Participants with severe psychiatric disorders.
• Participants 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
• Participants with previous liver transplantation.
• Participants with known or suspected hypersensitivity to albumin.
• Participants participating in another clinical study within 3 months prior to screening.
• Participants with active drug addiction (exceptions: active alcoholism or marijuana).
• In the opinion of the investigator, the participants may have compliance problems with the protocol and the procedures of the protocol.
• Participants with ongoing or recent variceal bleeding (participants can be included 2 weeks after hemorrhagic episode).
• Participants with septic shock at screening.
• Participants with ongoing spontaneous bacterial peritonitis (SBP) infection (participants can be included upon resolution).
• Participants with current infection of coronavirus disease of 2019 (COVID19), those who are less than 14 days post recovery, or those who have clinical signs and symptoms consistent with COVID19 infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Grifols, S.A.

INDUSTRY

Sponsor Role: collaborator

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Southern California Research Center

Coronado, California, United States

University of Miami Hospital

Miami, Florida, United States

Rutgers-New Jersey Medical School

Newark, New Jersey, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Missouri Hospital

Columbia, South Carolina, United States

Dallas VA Medical Center

Dallas, Texas, United States

McGuire VA Medical Center

Richmond, Virginia, United States

Université libre de Bruxelles

Brussels, , Belgium

Antwerp University Hospital

Edegem, , Belgium

UZ Leuven - Campus Gasthuisberg

Leuven, , Belgium

University Clinical Centre of the Republic Srpska, Clinic for Internal Diseases, Department of gastroenterology, hepatology and toxicology with internal medicine

Mostar, , Bosnia and Herzegovina

Dr. Abdulah Nakas General Hospital, Department of Internal Medicine, Department of Gastroenterohepatology

Sarajevo, , Bosnia and Herzegovina

Zenica Cantonal Hospital, Department of Internal Medicine with hemodialysis, Department of Gastroenterology and hepatology

Zenica, , Bosnia and Herzegovina

MHAT "Pazardzhik" Ltd

Pazardzhik, , Bulgaria

MHAT"Sv. Pantelymon"

Plovdiv, , Bulgaria

MHAT " Hadzhi Dimitar" Ltd

Sliven, , Bulgaria

MHAT Sliven to MMA Sofia

Sliven, , Bulgaria

MHAT "Sveta Sofia"

Sofia, , Bulgaria

UMHAT "Sveti Ivan Rilski"

Sofia, , Bulgaria

UMHATEM "N.I.Pirogov"

Sofia, , Bulgaria

First Private MHAT Vratsa

Vratsa, , Bulgaria

University Health Network - Toronto General Hospital

Toronto, , Canada

Hvidovre University Hospital

Hvidovre, , Denmark

Hôpital Minjoz - CHU Besaçon

Besançon, , France

Hôpital Henri Mondor-Creteil

Créteil, , France

CHU de Nice - Hôpital l'Archet 2

Nice, , France

CHRU de Strasbourg - Hôpital Hautepierre

Strasbourg, , France

Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse

Villejuif, , France

Charité - Universitaetsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Essen

Essen, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Universitätsklinikum Jena

Jena, , Germany

Magyar Honvédség Egészségügyi Központ Gasztroenterológiai Osztály

Budapest, , Hungary

Semmelweis Egyetem I. sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika

Budapest, , Hungary

Debreceni Egyetem Klinikai Központ Gasztroenterológiai Klinika

Debrecen, , Hungary

Markhot Ferenc Oktatókórház és Rendelőintézet

Eger, , Hungary

Albert Schweitzer Kórház

Hatvan, , Hungary

Azienda Ospedaliero-Universitaria di Bologna Policlinico - S.Orsola

Bologna, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Oddział Gastroenterologii i Hepatologii Uniwersyteckie Centrum Kliniczne im. prof.K.Gibińskiego SUM w Katowicach

Katowice, , Poland

SP ZOZ Szpital Uniwersytecki w Krakowie, Zakład Endoskopii SIV 31Aug22

Krakow, , Poland

Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego

Lodz, , Poland

Klinika Chorób Wewnętrznych, Diabetologii i Farmakologii Klinicznej, Centralny Szpital Kliniczny

Lodz, , Poland

Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego

Lublin, , Poland

ID Clinic

Mysłowice, , Poland

Klinika Gastroenterologii i Hepatologii z Pododdziałem Chorób Wewnętrznych Kliniczny Szpital Wojewodzki nr 1

Rzeszów, , Poland

Centrum Badań Klinicznych

Wroclaw, , Poland

Samodzielny Publiczny Szpital im.Papieza Jana Pawla II

Zamość, , Poland

Clinical Hospital Center "Dr Dragisa Misovic-Dedinje", Clinic for Internal Medicine, Gastroenterology Department

Belgrade, , Serbia

Clinical Hospital Center Zvezdara, Clinic for Internal Diseases, Clinical Department for Gastroenterology and Hepatology

Belgrade, , Serbia

University Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology

Belgrade, , Serbia

Military Medical Academy, Clinic for Gastroenterology and Hepatology

Belgrade, , Serbia

Clinical Hospital Center "Bezanijska Kosa", Clinic for Internal Medicine, Department for Gastroenterology and Hepatology

Belgrade, , Serbia

University Clinical Center Kragujevac, Clinic for Internal Medicine, Gastroenterohepatology Center

Kragujevac, , Serbia

'University Clinical Center Nis, Clinic for Gastroenterology and Hepatology

Niš, , Serbia

Institution: General Hospital Pančevo, Internal Diseases Department, Gastroenterology Section

Pančevo, , Serbia

'Health Center Uzice, Internal Diseases Department, Gastroenterology Section

Užice, , Serbia

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Puerta de Hierro Majadahonda

Majadahonda, , Spain

Hospital Marqués de Valdecilla

Santander, , Spain

Hospital Universitario Politecnico La Fe

Valencia, , Spain

Royal Free NHS Foundation Trust Hospital

London, Londong, United Kingdom

Countries

United States; Belgium; Bosnia and Herzegovina; Bulgaria; Canada; Denmark; France; Germany; Hungary; Italy; Poland; Serbia; Spain; United Kingdom

References

Fernandez J, Claria J, Amoros A, Aguilar F, Castro M, Casulleras M, Acevedo J, Duran-Guell M, Nunez L, Costa M, Torres M, Horrillo R, Ruiz-Del-Arbol L, Villanueva C, Prado V, Arteaga M, Trebicka J, Angeli P, Merli M, Alessandria C, Aagaard NK, Soriano G, Durand F, Gerbes A, Gustot T, Welzel TM, Salerno F, Banares R, Vargas V, Albillos A, Silva A, Morales-Ruiz M, Carlos Garcia-Pagan J, Pavesi M, Jalan R, Bernardi M, Moreau R, Paez A, Arroyo V. Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis. Gastroenterology. 2019 Jul;157(1):149-162. doi: 10.1053/j.gastro.2019.03.021. Epub 2019 Mar 22.

Reference Type: DERIVED

PMID: 30905652 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001789-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IG1601

Identifier Type: -

Identifier Source: org_study_id