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

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

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.

Study Overview

• Status: Completed
• Conditions: Decompensated Cirrhosis and Ascites
• Intervention / Treatment: Drug: Albutein 20%; Other: SMT

• Study Type: Interventional
• Enrollment (Actual): 410
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Université Libre de Bruxelles
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Leuven, Belgium, 3000
    • UZ Leuven - Campus Gasthuisberg
• Bosnia and Herzegovina
  • Mostar, Bosnia and Herzegovina, 88000
    • University Clinical Centre of the Republic Srpska, Clinic for Internal Diseases, Department of gastroenterology, hepatology and toxicology with internal medicine
  • Sarajevo, Bosnia and Herzegovina
    • Dr. Abdulah Nakas General Hospital, Department of Internal Medicine, Department of Gastroenterohepatology
  • Zenica, Bosnia and Herzegovina
    • Zenica Cantonal Hospital, Department of Internal Medicine with hemodialysis, Department of Gastroenterology and hepatology
• Bulgaria
  • Pazardzhik, Bulgaria, 4400
    • MHAT "Pazardzhik" Ltd
  • Plovdiv, Bulgaria, 4000
    • MHAT"Sv. Pantelymon"
  • Sliven, Bulgaria, 8800
    • MHAT " Hadzhi Dimitar" Ltd
  • Sliven, Bulgaria, 8800
    • MHAT Sliven to MMA Sofia
  • Sofia, Bulgaria, 1000
    • MHAT "Sveta Sofia"
  • Sofia, Bulgaria, 1000
    • UMHAT "Sveti Ivan Rilski"
  • Sofia, Bulgaria, 1000
    • UMHATEM "N.I.Pirogov"
  • Vratsa, Bulgaria, 3000
    • First Private MHAT Vratsa
• Canada
  • Toronto, Canada
    • University Health Network - Toronto General Hospital
• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital
• France
  • Besançon, France, 25000
    • Hôpital Minjoz - CHU Besaçon
  • Créteil, France, 94010
    • Hôpital Henri Mondor-Creteil
  • Nice, France, CS 23079
    • CHU de Nice - Hôpital L'Archet 2
  • Strasbourg, France, 67200
    • CHRU de Strasbourg - Hôpital Hautepierre
  • Villejuif, France, 94804
    • Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitaetsmedizin Berlin
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Jena, Germany, 7740
    • Universitatsklinikum Jena
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvédség Egészségügyi Központ Gasztroenterológiai Osztály
  • Budapest, Hungary, 1082
    • Semmelweis Egyetem I. sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Központ Gasztroenterológiai Klinika
  • Eger, Hungary, 3300
    • Markhot Ferenc Oktatokorhaz és Rendelointezet
  • Hatvan, Hungary, 3000
    • Albert Schweitzer Kórház
• Italy
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico - S.Orsola
  • Milano, Italy, 20162
    • Asst Grande Ospedale Metropolitano Niguarda
  • Padova, Italy, 35131
    • Azienda Ospedaliera di Padova
• Poland
  • Katowice, Poland, 40-751
    • Oddział Gastroenterologii i Hepatologii Uniwersyteckie Centrum Kliniczne im. prof.K.Gibińskiego SUM w Katowicach
  • Kraków, Poland, 30-688
    • SP ZOZ Szpital Uniwersytecki w Krakowie, Zakład Endoskopii SIV 31Aug22
  • Lublin, Poland, 20954
    • Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego
  • Mysłowice, Poland, 41-400
    • ID Clinic
  • Rzeszów, Poland
    • Klinika Gastroenterologii i Hepatologii z Pododdziałem Chorób Wewnętrznych Kliniczny Szpital Wojewodzki nr 1
  • Wrocław, Poland, 51-162
    • Centrum Badan Klinicznych
  • Zamość, Poland, 22-400
    • Samodzielny Publiczny Szpital im.Papieza Jana Pawla II
  • Łódź, Poland, 90-153
    • Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego
  • Łódź, Poland, 92-216
    • Klinika Chorób Wewnętrznych, Diabetologii i Farmakologii Klinicznej, Centralny Szpital Kliniczny
• Serbia
  • Belgrad, Serbia, 11040
    • Military Medical Academy, Clinic for Gastroenterology and Hepatology
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center "Dr Dragisa Misovic-Dedinje", Clinic for Internal Medicine, Gastroenterology Department
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zvezdara, Clinic for Internal Diseases, Clinical Department for Gastroenterology and Hepatology
  • Belgrade, Serbia, 11000
    • University Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center "Bezanijska Kosa", Clinic for Internal Medicine, Department for Gastroenterology and Hepatology
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac, Clinic for Internal Medicine, Gastroenterohepatology Center
  • Niš, Serbia, 18000
    • 'University Clinical Center Nis, Clinic for Gastroenterology and Hepatology
  • Pančevo, Serbia, 26101
    • Institution: General Hospital Pančevo, Internal Diseases Department, Gastroenterology Section
  • Užice, Serbia, 31000
    • 'Health Center Uzice, Internal Diseases Department, Gastroenterology Section
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Majadahonda, Spain
    • Hospital Puerta de Hierro Majadahonda
  • Santander, Spain, 39008
    • Hospital Marques de Valdecilla
  • Valencia, Spain
    • Hospital Universitario Politecnico La Fe
• United Kingdom
  • Londong
    • London, Londong, United Kingdom, NW3 2QG
      • Royal Free NHS Foundation Trust Hospital
• United States
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers-New Jersey Medical School
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Columbia, South Carolina, United States, 65201
      • University of Missouri Hospital
  • Texas
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Albutein 20%; Injectable solution; Other: SMT; Participants received SMT according to institution standards for the management of decompensated cirrhosis.
Active Comparator: SMT; Participants received SMT up to 12 months as per institution standards for the management of decompensated cirrhosis.	Other: SMT; Participants received SMT according to institution standards for the management of decompensated cirrhosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Liver Transplantation or Death Through 3 Months After Randomization: Percentage of Participants With an Event	Time to 3-months 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 91 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 91, 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 91) / (number of participants in the ITT group)].	Up to Day 91
Time to Liver Transplantation or Death Through 6 Months After Randomization: Percentage of Participants With an Event	Time to 6-months 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 181 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 181, 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 181) / (number of participants in the ITT group)].	Up to Day 181
Time to Death Through 3 Months After Randomization: Percentage of Participants With an Event	Time to 3-months survival was calculated as the earlier of [(date of death) - randomization date + 1] for those participants who died within the analysis period of 91 days. Participants who did not die within the analysis period were censored at the earlier of the date of last contact or analysis 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 death, these events if reported before the analysis cut-off Day 91 of this endpoint, were considered. The percentage of participants with events (death) without censoring participants who underwent liver transplantation within the analysis period were reported. The percentage of participants was calculated as [(participants with an event up to the analysis cut-off Day 91) / (number of participants in the ITT group)].	Up to Day 91
Time to Death Through 6 Months After Randomization: Percentage of Participants With an Event	Time to 6-months survival was calculated as the earlier of [(date of death) - randomization date + 1] for those participants who died within the analysis period of 181 days. Participants who did not die within the analysis period were censored at the earlier of the date of last contact or analysis 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 death, these events if reported before the analysis cut-off Day 181 of this endpoint, were considered. The percentage of participants with events (death) without censoring participants who underwent liver transplantation within the analysis period were reported. The percentage of participants was calculated as [(participants with an event up to the analysis cut-off Day 181) / (number of participants in the ITT group)].	Up to Day 181
Time to Death Through 1 Year After Randomization: Percentage of Participants With an Event	Time to 1 year survival was calculated as the earlier of [(date of death) - randomization date + 1] for those participants who died within the analysis period of 361 days. Participants who did not die within the analysis period were censored at the earlier of the date of last contact or analysis 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 death, these events if reported before the analysis cut-off Day 361 of this endpoint, were considered. The percentage of participants with events (death) without censoring participants who underwent liver transplantation within the analysis period were reported. 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
Total Number of Paracenteses Through 1 Year After Randomization	Paracenteses is a medical procedure used to remove excess fluid from the abdominal cavity. For each participant, the total number of reported paracenteses on treatment was calculated. Number of paracenteses per participant while on treatment was reported.	Up to Day 361
Number of Participants With Refractory Ascites According to the International Club of Ascites (ICA) Through 1 Year After Randomization	Refractory Ascites was defined as ascites that cannot be mobilized, or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic, or the development of diuretic-induced complications that preclude the use of an effective diuretic dosage treatment. Incidence of refractory ascites occurring on treatment was defined as any incidence that occurred with a start date/time on or after the participants date/time of randomization (for SMT Alone group) or commencement of Albutein (SMT+ Albutein 20% group) treatment.	Up to Day 361

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC
• Collaborators: Instituto Grifols, S.A.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Actual): May 21, 2024
• Study Completion (Actual): May 21, 2024

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites
• Other Study ID Numbers: IG1601; 2016-001789-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No