Short-term Survival of Subjects With Acute-on-chronic Liver Failure After Plasma Exchange With Human Serum Albumin 5%

NCT03702920 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: IG1407
• Study Type: interventional
• Target: 275
• Locations: 10 countries
• Sites: 40

Brief Summary

This is a Phase 3, multicenter, randomized, controlled, parallel-group, open-label study to evaluate the effects of plasma exchange using human serum albumin 5% (PE-A 5%) in acute-on-chronic liver failure (ACLF) subjects. The study will involve approximately 40 study centers in the United States, Canada, and Europe with expertise in the management of subjects with ACLF. Subjects with ACLF at a high risk of hospital mortality will be enrolled. The study will consist of a Screening Period during which subjects will be randomized (1:1) to receive either standard medical treatment (SMT) + PE-A 5% (treatment group) or SMT only (control group), followed by a Treatment Period, and a Follow-up Period. The Treatment Period for subjects in the SMT+ PE-A 5% treatment group will be between 7 and 17 days, depending on ACLF evolution. The Treatment Period for subjects in the SMT control group will be a minimum of 7 days for all subjects and up to 17 days depending on the ACLF evolution. Subjects in this group will receive SMT according to the institution's standards. The Follow-up Period for subjects in both groups will be 90 days.

Conditions

Acute-On-Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• Time to death through Day 90

  Time to death through Day 90 after randomization of SMT+PE-A 5% versus SMT alone

  Day 1 to Day 90

Secondary Outcomes (2)

• Time to transplant or death through Day 90

  Day 1 to Day 90

• Time to death through Day 28

  Day 1 to Day 28

Study Arms (2)

SMT+ PE-A 5%

EXPERIMENTAL

PE-A 5% will be performed using 5% albumin (Albutein 5%) as the main replacement fluid administered intravenously.

Biological: SMT + PE-A 5%

Standard Medical Treatment (SMT)

ACTIVE COMPARATOR

Standard medical treatment (SMT) will be administered according to institution standards.

Other: Standard Medical Treatment

Interventions

SMT + PE-A 5% BIOLOGICAL

Plasma exchange treatment (PE-A 5%) will be performed using 5% albumin solution (Albutein 5%). Fresh frozen plasma will be given to prevent coagulopathy. IVIGs will be administered intravenously to prevent the development of hypogammaglobulinemia and infection.

Also known as: Albutein 5%

SMT+ PE-A 5%

Standard Medical Treatment OTHER

Standard medical treatment according to the institution's standard practice

Also known as: SMT

Standard Medical Treatment (SMT)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female cirrhotic subjects between 18 and 79 years of age.
• Subjects with ACLF-1b, ACLF-2, or ACLF-3a detected either at admission or during hospitalization (must be ACLF-1b, -2, or -3a within the Screening Period \[a maximum of 10 days\]).
• 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.
• In case of HE, informed consent will be provided by a relative or a legally authorized representative if the subject is considered incompetent to consent.

You may not qualify if:

• Subjects without ACLF.
• Subjects with ACLF-1a or ACLF-3b (See Table 2-1 for ACLF grades) after the Screening Period.
• Subjects with ACLF for more than 10 days prior to randomization.
• Subjects with acute or subacute liver failure without underlying cirrhosis.
• Subjects with septic shock requiring use of norepinephrine (\> 0.3 mcg/kg/min) or need for a second vasopressor (including terlipressin).
• Subjects with active bacterial or fungal infection: who have received less than 24h of appropriate antibiotic treatment.
• Subjects with severe respiratory failure with PaO2/FiO2 ≤200.
• Subjects with active or recent bleeding (unless controlled for \>48 hours).
• Subjects with severe thrombocytopenia (≤20×109/L) (based on local laboratory assessment).
• Subjects with chronic renal failure and currently receiving hemodialysis.
• Evidence of current locally advanced or metastatic malignancy. Subjects with hepatocellular carcinoma within the Milan criteria (1 nodule ≤5 cm or 3 nodules ≤3 cm \[Appendix 5\]), non-melanocytic skin cancer, and controlled breast or prostate cancer, can be included).
• Subjects with severe chronic heart failure (New York Heart Association \[NYHA\] class III or IV).
• Subjects with severe pulmonary disease (Global Obstructive Lung Disease \[GOLD\] stage III or IV).
• Subjects with severe myopathy as defined clinically.
• Subjects with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection.

Sponsors & Collaborators

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

Study Sites (40)

University of Alabama at Birmingham (UAB) Hospital

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas

Kansas City, Kansas, 66045, United States

Location

Rutgers-New Jersey Medical School

Newark, New Jersey, 07101, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Mayo Clinic Rochester

Rochester, New York, 55905, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Aurora Health Care, Inc.

Milwaukee, Wisconsin, 53215, United States

Location

Medical University of Vienna

Vienna, A-1090, Austria

Location

Université libre de Bruxelles

Brussels, 1070, Belgium

Location

UZ Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Rigshospitalet

Copenhagen, Denmark

Location

Hôpital Beaujon

Clichy, 92110, France

Location

Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse

Villejuif, 94804, France

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 4103, Germany

Location

Klinikum der Universitaet Muenchen

München, 81377, Germany

Location

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Milano Hospital Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico Umberto I

Roma, 161, Italy

Location

Centro Hospitalar Lisboa Norte

Lisbon, 1649-028, Portugal

Location

Centro Hospitalar do Porto

Porto, Portugal

Location

Hospital Universitario del Valle Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Royal Free NHS Foundation Trust Hospital

London, NW3 2QG, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Nottingham University Hospital

Nottingham, NG72UH, United Kingdom

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

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: October 9, 2018
• First Posted: October 11, 2018
• Study Start: February 21, 2019
• Primary Completion: April 14, 2025
• Study Completion: April 14, 2025
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); GB (3); DE (5); FR (2); IT (5); DK (1); ES (4); PT (2); US (15); BE (2)