Clinical trial NCT03451292: Effects of Long-Term Administration of Human Albumin in Participants With Decompensated Cirrhosis and Ascites
Official title: Prevention of Mortality With Long-Term Administration of Human Albumin in Subjects With Decompensated Cirrhosis and Ascites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Decompensated Cirrhosis and Ascites
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Instituto Grifols, S.A.
First posted: 2018-03-01
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Time to Liver Transplantation or Death Through 1 Year After Randomization: Percentage of Participants With an Event
timeFrame: Up to Day 361
Secondary outcomes:
measure: Time to Liver Transplantation or Death Through 3 Months After Randomization: Percentage of Participants With an Event
timeFrame: Up to Day 91
measure: Time to Liver Transplantation or Death Through 6 Months After Randomization: Percentage of Participants With an Event
timeFrame: Up to Day 181
measure: Time to Death Through 3 Months After Randomization: Percentage of Participants With an Event
timeFrame: Up to Day 91
measure: Time to Death Through 6 Months After Randomization: Percentage of Participants With an Event
timeFrame: Up to Day 181
measure: Time to Death Through 1 Year After Randomization: Percentage of Participants With an Event
timeFrame: Up to Day 361
measure: Total Number of Paracenteses Through 1 Year After Randomization
timeFrame: Up to Day 361
measure: Number of Participants With Refractory Ascites According to the International Club of Ascites (ICA) Through 1 Year After Randomization
timeFrame: Up to Day 361
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Newark
country: United States
facility: Rutgers-New Jersey Medical School
state: New Jersey
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Columbia
country: United States
facility: University of Missouri Hospital
state: South Carolina
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Bruxelles
country: Belgium
facility: Université libre de Bruxelles
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic Srpska, Clinic for Internal Diseases, Department of gastroenterology, hepatology and toxicology with internal medicine
city: Sarajevo
country: Bosnia and Herzegovina
facility: Dr. Abdulah Nakas General Hospital, Department of Internal Medicine, Department of Gastroenterohepatology
city: Zenica
country: Bosnia and Herzegovina
facility: Zenica Cantonal Hospital, Department of Internal Medicine with hemodialysis, Department of Gastroenterology and hepatology
city: Pazardzhik
country: Bulgaria
facility: MHAT "Pazardzhik" Ltd
city: Plovdiv
country: Bulgaria
facility: MHAT"Sv. Pantelymon"
city: Sliven
country: Bulgaria
facility: MHAT " Hadzhi Dimitar" Ltd
city: Sliven
country: Bulgaria
facility: MHAT Sliven to MMA Sofia
city: Sofia
country: Bulgaria
facility: MHAT "Sveta Sofia"
city: Sofia
country: Bulgaria
facility: UMHAT "Sveti Ivan Rilski"
city: Sofia
country: Bulgaria
facility: UMHATEM "N.I.Pirogov"
city: Vratsa
country: Bulgaria
facility: First Private MHAT Vratsa
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
city: Besançon
country: France
facility: Hôpital Minjoz - CHU Besaçon
city: Créteil
country: France
facility: Hôpital Henri Mondor-Creteil
city: Nice
country: France
facility: CHU de Nice - Hôpital l'Archet 2
city: Strasbourg
country: France
facility: CHRU de Strasbourg - Hôpital Hautepierre
city: Villejuif
country: France
facility: Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse
city: Berlin
country: Germany
facility: Charité - Universitaetsmedizin Berlin
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ Gasztroenterológiai Osztály
city: Budapest
country: Hungary
facility: Semmelweis Egyetem I. sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ Gasztroenterológiai Klinika
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatókórház és Rendelőintézet
city: Hatvan
country: Hungary
facility: Albert Schweitzer Kórház
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico - S.Orsola
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Katowice
country: Poland
facility: Oddział Gastroenterologii i Hepatologii Uniwersyteckie Centrum Kliniczne im. prof.K.Gibińskiego SUM w Katowicach
city: Kraków
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie, Zakład Endoskopii SIV 31Aug22
city: Lublin
country: Poland
facility: Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego
city: Mysłowice
country: Poland
facility: ID Clinic
city: Rzeszów
country: Poland
facility: Klinika Gastroenterologii i Hepatologii z Pododdziałem Chorób Wewnętrznych Kliniczny Szpital Wojewodzki nr 1
city: Wrocław
country: Poland
facility: Centrum Badań Klinicznych
city: Zamość
country: Poland
facility: Samodzielny Publiczny Szpital im.Papieza Jana Pawla II
city: Łódź
country: Poland
facility: Oddział Kliniczny Gastroenterologii Ogólnej i Onkologicznej, Uniwersytecki Szpital Kliniczny im. Barlickiego
city: Łódź
country: Poland
facility: Klinika Chorób Wewnętrznych, Diabetologii i Farmakologii Klinicznej, Centralny Szpital Kliniczny
city: Belgrade
country: Serbia
facility: Clinical Hospital Center "Dr Dragisa Misovic-Dedinje", Clinic for Internal Medicine, Gastroenterology Department
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara, Clinic for Internal Diseases, Clinical Department for Gastroenterology and Hepatology
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center "Bezanijska Kosa", Clinic for Internal Medicine, Department for Gastroenterology and Hepatology
city: Belgrad
country: Serbia
facility: Military Medical Academy, Clinic for Gastroenterology and Hepatology
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac, Clinic for Internal Medicine, Gastroenterohepatology Center
city: Niš
country: Serbia
facility: 'University Clinical Center Nis, Clinic for Gastroenterology and Hepatology
city: Pančevo
country: Serbia
facility: Institution: General Hospital Pančevo, Internal Diseases Department, Gastroenterology Section
city: Užice
country: Serbia
facility: 'Health Center Uzice, Internal Diseases Department, Gastroenterology Section
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitario Politecnico La Fe
city: London
country: United Kingdom
facility: Royal Free NHS Foundation Trust Hospital
state: Londong
Study officials:
References:
citation: 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.