Effects of Long-Term Administration of Human Albumin in Subjects 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 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Decompensated Cirrhosis and Ascites
• Intervention / Treatment: Drug: Albutein 20% Injectable Solution; Other: Standard medical treatment

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

Contacts and Locations

• Study Contact: Name: Mireia Torres; Phone Number: +34 93 5710500; Email: approach_preciosa@grifols.com

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
    • Universitatsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitatsklinikum 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 Es 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 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.

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: Standard Medical Treatment + Albutein 20%; Standard Medical Treatment plus Albutein 20% administrations	Drug: Albutein 20% Injectable Solution; 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.; Other: Standard medical treatment; Subjects will receive SMT according to published guidelines for the management of decompensated cirrhosis.
Active Comparator: Standard Medical Treatment; The sites will follow the Standard Medical Treatment as per their Standard of Care.	Other: Standard medical treatment; Subjects will receive SMT according to published guidelines for the management of decompensated cirrhosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

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 (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 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 (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites
• Other Study ID Numbers: IG1601

Drug and device information, study documents

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