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

Decompensated Cirrhosis and Ascites Clinical Trial

— PRECIOSA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03451292
• Other study ID #: IG1601
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 24, 2018
• Est. completion date: May 2024

Study information

• Verified date: May 2024
• Source: Grifols Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 410
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Ascites
• Decompensated Cirrhosis and Ascites
• Fibrosis
• Liver Cirrhosis

Intervention

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.

Locations

Country	Name	City	State
Belgium	Université libre de Bruxelles	Bruxelles
Belgium	Antwerp University Hospital	Edegem
Belgium	UZ Leuven - Campus Gasthuisberg	Leuven
Bosnia and Herzegovina	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
Bulgaria	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
Canada	University Health Network - Toronto General Hospital	Toronto
Denmark	Hvidovre University Hospital	Hvidovre
France	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
Germany	Charité - Universitaetsmedizin Berlin	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Jena	Jena
Hungary	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 Rendelointézet	Eger
Hungary	Albert Schweitzer Kórház	Hatvan
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico - S.Orsola	Bologna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Azienda Ospedaliera di Padova	Padova
Poland	Oddzial Gastroenterologii i Hepatologii Uniwersyteckie Centrum Kliniczne im. prof.K.Gibinskiego SUM w Katowicach	Katowice
Poland	SP ZOZ Szpital Uniwersytecki w Krakowie, Zaklad Endoskopii SIV 31Aug22	Kraków
Poland	Klinika Chorób Wewnetrznych, Diabetologii i Farmakologii Klinicznej, Centralny Szpital Kliniczny	Lódz
Poland	Oddzial Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego	Lódz
Poland	Oddzial Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego	Lublin
Poland	ID Clinic	Myslowice
Poland	Klinika Gastroenterologii i Hepatologii z Pododdzialem Chorób Wewnetrznych Kliniczny Szpital Wojewodzki nr 1	Rzeszów
Poland	Centrum Badan Klinicznych	Wroclaw
Poland	Samodzielny Publiczny Szpital im.Papieza Jana Pawla II	Zamosc
Serbia	Military Medical Academy, Clinic for Gastroenterology and Hepatology	Belgrad
Serbia	Clinical Hospital Center "Bezanijska Kosa", Clinic for Internal Medicine, Department for Gastroenterology and Hepatology	Belgrade
Serbia	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	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 Pancevo, Internal Diseases Department, Gastroenterology Section	Pancevo
Serbia	'Health Center Uzice, Internal Diseases Department, Gastroenterology Section	Užice
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	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
United Kingdom	Royal Free NHS Foundation Trust Hospital	London	Londong
United States	University of Missouri Hospital	Columbia	South Carolina
United States	Southern California Research Center	Coronado	California
United States	Dallas VA Medical Center	Dallas	Texas
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	McGuire VA Medical Center	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC	Instituto Grifols, S.A.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Time to death through 3 months after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone		3 months
Secondary	Time to death through 6 months after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone		6 months
Secondary	Time to death through 1 year after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone		12 months
Secondary	Total number of paracenteses through 1 year after randomization in subjects receiving SMT + Albutein 20% administration versus subjects receiving SMT alone		12 months
Secondary	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