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

May 8, 2026 updated by: Instituto Grifols, S.A.

Effects of Plasma Exchange With Human Serum Albumin 5% (PE-A 5%) on Short-term Survival in Subjects With "Acute-On-Chronic Liver Failure" (ACLF) at High Risk of Hospital Mortality

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Approximately 380 subjects with cirrhosis, ACLF, and high risk of hospital mortality (ACLF-1b, ACLF-2, or ACLF-3a) will be included in this study after obtaining written informed consent. In case of hepatic encephalopathy (HE), written informed consent will be obtained from a relative or a legally authorized representative if the subject is considered incompetent to consent.

Randomization of subjects will be stratified by region (European Union [EU] or North America [NA]) and the 3 ACLF grades (ACLF-1b, ACLF-2, or ACLF-3a). Within each stratum (ie, each unique combination of region and ACLF grade), subjects will be randomized in a 1:1 ratio into 2 treatment groups below:

  • SMT+PE-A 5% (treatment group)
  • SMT (control group)

SMT + PE-A 5% Treatment Group:

PE-A 5% will be performed using 5% albumin (Albutein® 5%) as the main replacement fluid administered intravenously. Fresh frozen plasma (FFP) will be given after each PE-A 5% session to prevent coagulopathy. SMT in addition to PE-A 5% will be administered according to institution standard practice.

The exact number of sessions will be determined by the pattern of response (achieving complete response or no improvement/deterioration of ACLF) to PE-A 5% therapy. IVIGs will be administered to prevent the development of hypogammaglobulinemia and infection.

SMT Control Group:

SMT will be administered according to institution standards practices.

Subjects in both the SMT+ PE-A 5% treatment group and the SMT control group will be followed for 90 days after randomization. During the entire study, the safety of both groups will be monitored by a Data Safety Monitoring Board.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
274

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Vienna, Austria, A-1090
        • Medical University of Vienna
  • Belgium
      • Brussels, Belgium, 1070
        • Université libre de Bruxelles
      • Leuven, Belgium, 3000
        • UZ Leuven - Campus Gasthuisberg
  • France
      • Clichy, France, 92110
        • Hôpital Beaujon
      • Villejuif, France, 94804
        • Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse
  • Germany
      • Frankfurt, Germany, 60590
        • Universitätsklinikum Frankfurt
      • Hanover, Germany, 30625
        • Hannover Medical School
      • Leipzig, Germany, 4103
        • Universitaetsklinikum Leipzig
      • München, Germany, 81377
        • Klinikum der Universitaet Muenchen
  • Italy
      • Milan, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda
      • Padova, Italy, 35128
        • Azienda Ospedaliera di Padova
    • Milan
      • Milan, Milan, Italy, 20122
        • Milano Hospital Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
    • Roma
      • Roma, Roma, Italy, 161
        • Azienda Ospedaliero-Universitaria Policlinico Umberto I
  • Portugal
      • Porto, Portugal
        • Centro Hospitalar do Porto
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 08035
        • Hospital Universitario del Valle Hebron
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • King's College Hospital NHS Foundation Trust
    • London
      • London, London, United Kingdom, NW3 2QG
        • Royal Free NHS Foundation Trust Hospital
    • Nottingham
      • Nottingham, Nottingham, United Kingdom, NG72UH
        • Nottingham University Hospital
  • United States
    • California
      • Coronado, California, United States, 92118
        • Southern California Research Center
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • New Jersey
      • Newark, New Jersey, United States, 07101
        • Rutgers-New Jersey Medical School
    • New York
      • Rochester, New York, United States, 55905
        • Mayo Clinic Rochester
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Virginia
      • Richmond, Virginia, United States, 23249
        • McGuire VA Medical Center
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Health Care, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Subjects without ACLF.
  • Subjects with ACLF-1a or ACLF-3b after the Screening Period.
  • Subjects fulfilling inclusion criteria that improve to no ACLF or to ACLF-1a or worsen to ACLF-3b during the Screening Period (between initial evaluation and time of randomization).
  • 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 (≤20×10^9/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), 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.
  • Females who are pregnant, breastfeeding, or if of childbearing potential, unwilling to practice a highly effective method of contraception.
  • Subjects with previous liver transplantation.
  • Subjects receiving anti-platelet or anti-coagulant therapy (LMWH for DVT prophylaxis is allowed).
  • Participation in another clinical study within at least 30 days prior to screening.
  • Subjects with active drug addiction (exceptions: active alcoholism or marijuana).
  • Subjects with a do-not-resuscitate order.
  • In the opinion of the investigator, the subject may have compliance problems with the protocol and the procedures of the protocol.
  • Subjects with current infection of COVID-19, those who are less than 14 days post recovery or those who have clinical signs and symptoms consistent with COVID-19 infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SMT + PE-A 5%
PE-A 5% will be performed using 5% albumin (Albutein 5%) as the main replacement fluid administered intravenously. SMT in addition to PE-A 5% will be administered according to institution standards practice.
Biological: SMT + PE-A 5%
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. SMT in addition to PE-A 5% according to the institution's standard practice.
Other Names:
  • Albutein 5%
Active Comparator: SMT Alone
Standard medical treatment (SMT) will be administered according to institution standard practices.
Other: Standard Medical Treatment
Standard medical treatment according to the institution's standard practice
Other Names:
  • SMT

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to Death Without a Prior Liver Transplant Through Day 90 After Randomization
Time Frame: Up to Day 90
Time to 90-day overall survival was to be calculated as [(date of death) - randomization date] for those participants who died without having liver transplant on or prior to 90 days. Participants who did not die, or had a liver transplant before death were to have their time to event censored at the earlier of date of last contact, liver transplant date or cut-off date. 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) / (number of participants in the ITT group)].
Up to Day 90

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Liver Transplant or Death Through Day 90 After Randomization
Time Frame: Day 1 to Day 90
Time to 90-day liver transplant free survival was calculated as [the earlier of the date of liver transplantation or date of death - randomization date for those participants who died or had a liver transplant on or prior to 90 days]. Participants who neither died nor had a liver transplant, were had their time to event censored at the earlier of date of last contact or cut-off date. 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) / (number of participants in the ITT group)].
Day 1 to Day 90
Time to Death Without a Prior Liver Transplant Through Day 28 After Randomization
Time Frame: Day 1 to Day 28
Time to 28-day overall survival was calculated as [date of death - randomization date] for those participants who died without having liver transplant on or prior to 28 days. Participants who did not die, or had a liver transplant before death were to have their time to event censored at the earlier of date of last contact, liver transplant date or cut-off date. 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) / (number of participants in the ITT group)].
Day 1 to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto Grifols, S.A.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Instituto Grifols, S.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 17, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 14, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 14, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 11, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IG1407

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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