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

NCT03451292 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: IG16012016-001789-28
• Study Type: interventional
• Target: 410
• Locations: 14 countries
• Sites: 66

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

Outcome Measures

Primary Outcomes (1)

• Time to Liver Transplantation or Death Through 1 Year After Randomization: Percentage of Participants With an Event

  Time to one-year transplant-free survival was calculated as earlier of \[(date of liver transplantation or date of death) - randomization date + 1\] for participants who died or had liver transplant within the analysis period of 361 days. Participants who neither died nor had liver transplant within analysis period had their time to event censored at earlier of date of last contact or cut-off date. Participants who terminated early for reasons other than death were followed up at months 3, 6, and 12 to collect information on liver transplantation and death, these events if reported by cut-off Day 361, were considered for the endpoint. The percentage of participants with events are presented. The percentage of participants was calculated as \[(participants with an event up to the analysis cut-off Day 361) / (number of participants in the ITT group)\].

  Up to Day 361

Secondary Outcomes (7)

• Time to Liver Transplantation or Death Through 3 Months After Randomization: Percentage of Participants With an Event

  Up to Day 91

• Time to Liver Transplantation or Death Through 6 Months After Randomization: Percentage of Participants With an Event

  Up to Day 181

• Time to Death Through 3 Months After Randomization: Percentage of Participants With an Event

  Up to Day 91

• Time to Death Through 6 Months After Randomization: Percentage of Participants With an Event

  Up to Day 181

• Time to Death Through 1 Year After Randomization: Percentage of Participants With an Event

  Up to Day 361

Study Arms (2)

SMT + Albutein 20%

EXPERIMENTAL

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.

Drug: Albutein 20%; Other: SMT

SMT

ACTIVE COMPARATOR

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

Other: SMT

Interventions

Albutein 20% DRUG

Injectable solution

SMT + Albutein 20%

SMT OTHER

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

SMT; SMT + Albutein 20%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead
• Instituto Grifols, S.A.: collaborator

Study Sites (66)

Southern California Research Center

Coronado, California, 92118, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Rutgers-New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Missouri Hospital

Columbia, South Carolina, 65201, United States

Location

Dallas VA Medical Center

Dallas, Texas, 75216, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Université libre de Bruxelles

Brussels, 1070, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

UZ Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

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

Mostar, 88000, Bosnia and Herzegovina

Location

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

Sarajevo, Bosnia and Herzegovina

Location

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

Zenica, Bosnia and Herzegovina

Location

MHAT "Pazardzhik" Ltd

Pazardzhik, 4400, Bulgaria

Location

MHAT"Sv. Pantelymon"

Plovdiv, 4000, Bulgaria

Location

MHAT " Hadzhi Dimitar" Ltd

Sliven, 8800, Bulgaria

Location

MHAT Sliven to MMA Sofia

Sliven, 8800, Bulgaria

Location

MHAT "Sveta Sofia"

Sofia, 1000, Bulgaria

Location

UMHAT "Sveti Ivan Rilski"

Sofia, 1000, Bulgaria

Location

UMHATEM "N.I.Pirogov"

Sofia, 1000, Bulgaria

Location

First Private MHAT Vratsa

Vratsa, 3000, Bulgaria

Location

University Health Network - Toronto General Hospital

Toronto, Canada

Location

Hvidovre University Hospital

Hvidovre, 2650, Denmark

Location

Hôpital Minjoz - CHU Besaçon

Besançon, 25000, France

Location

Hôpital Henri Mondor-Creteil

Créteil, 94010, France

Location

CHU de Nice - Hôpital l'Archet 2

Nice, CS 23079, France

Location

CHRU de Strasbourg - Hôpital Hautepierre

Strasbourg, 67200, France

Location

Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse

Villejuif, 94804, France

Location

Charité - Universitaetsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Jena

Jena, 7740, Germany

Location

Magyar Honvédség Egészségügyi Központ Gasztroenterológiai Osztály

Budapest, 1062, Hungary

Location

Semmelweis Egyetem I. sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika

Budapest, 1082, Hungary

Location

Debreceni Egyetem Klinikai Központ Gasztroenterológiai Klinika

Debrecen, 4032, Hungary

Location

Markhot Ferenc Oktatókórház és Rendelőintézet

Eger, 3300, Hungary

Location

Albert Schweitzer Kórház

Hatvan, 3000, Hungary

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico - S.Orsola

Bologna, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35131, Italy

Location

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

Katowice, 40-751, Poland

Location

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

Krakow, 30-688, Poland

Location

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

Lodz, 90-153, Poland

Location

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

Lodz, 92-216, Poland

Location

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

Lublin, 20954, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

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

Rzeszów, Poland

Location

Centrum Badań Klinicznych

Wroclaw, 51-162, Poland

Location

Samodzielny Publiczny Szpital im.Papieza Jana Pawla II

Zamość, 22-400, Poland

Location

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

Belgrade, 11000, Serbia

Location

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

Belgrade, 11000, Serbia

Location

University Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology

Belgrade, 11000, Serbia

Location

Military Medical Academy, Clinic for Gastroenterology and Hepatology

Belgrade, 11040, Serbia

Location

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

Belgrade, 11080, Serbia

Location

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

Kragujevac, 34000, Serbia

Location

'University Clinical Center Nis, Clinic for Gastroenterology and Hepatology

Niš, 18000, Serbia

Location

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

Pančevo, 26101, Serbia

Location

'Health Center Uzice, Internal Diseases Department, Gastroenterology Section

Užice, 31000, Serbia

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, Spain

Location

Hospital Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Politecnico La Fe

Valencia, Spain

Location

Royal Free NHS Foundation Trust Hospital

London, Londong, NW3 2QG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30905652 DERIVED

MeSH Terms

Conditions

Ascites

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Mireia Torres
• Organization: Instituto Grifols, S.A.

approach_preciosa@grifols.com

+34 93 5710500

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: March 1, 2018
• Study Start: July 24, 2018
• Primary Completion: May 21, 2024
• Study Completion: May 21, 2024
• Last Updated: June 6, 2025
• Results First Posted: June 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); DE (4); CA (1); IT (3); SE (9); ES (7); BE (3); BO (3); FR (5); GB (1); PL (9); BU (8); HU (5); DK (1)