Acute-On-Chronic Liver FailurePhase 3APACHENCT03702920
Short-term Survival of Subjects With Acute-on-chronic Liver Failure After Plasma Exchange With Human Serum Albumin 5%
A Phase 3 study testing SMT + PE-A 5% and Standard Medical Treatment in people with Acute-On-Chronic Liver Failure, run by Instituto Grifols, S.A. at 30 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure
- What is being tested?
- SMT + PE-A 5% and Standard Medical Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 274 participants
- Where
- 30 sitesin 9 countries
- Study dates
- 17 Jun 2019to 14 Apr 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 24Show fewer
- 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.
Trial locations and contacts
30 sites in 9 countries.
30 sites in 9 countries
United States10 sites
Emory University
Atlanta, Georgia, 30322
Southern California Research Center
Coronado, California, 92118
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Aurora Health Care, Inc.
Milwaukee, Wisconsin, 53215
Rutgers-New Jersey Medical School
Newark, New Jersey, 07101
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
McGuire VA Medical Center
Richmond, Virginia, 23249
Mayo Clinic Rochester
Rochester, New York, 55905
University of Washington Medical Center
Seattle, Washington, 98195
Germany4 sites
Universitätsklinikum Frankfurt
Frankfurt, 60590
Hannover Medical School
Hanover, 30625
Universitaetsklinikum Leipzig
Leipzig, 4103
Klinikum der Universitaet Muenchen
München, 81377
Italy4 sites
Milano Hospital Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Milan, Milan, 20122
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
Azienda Ospedaliera di Padova
Padova, 35128
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Roma, Roma, 161
Spain3 sites
Hospital Universitario del Valle Hebron
Barcelona, 08035
Hospital Clínic de Barcelona
Barcelona, 08036
Hospital Universitario Ramón y Cajal
Madrid, 28034
United Kingdom3 sites
Royal Free NHS Foundation Trust Hospital
London, London, NW3 2QG
King's College Hospital NHS Foundation Trust
London, SE5 9RS
Nottingham University Hospital
Nottingham, Nottingham, NG72UH
Belgium2 sites
Université libre de Bruxelles
Brussels, 1070
UZ Leuven - Campus Gasthuisberg
Leuven, 3000
France2 sites
Hôpital Beaujon
Clichy, 92110
Centre Hépato-Biliaire - Hôpital Universitaire Paul Brousse
Villejuif, 94804
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Acute-On-Chronic Liver Failure
- Being tested
- SMT + PE-A 5%, Standard Medical Treatment
- Medical subject headings
- Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SMT + PE-A 5%Biological
Also called Albutein 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.
Standard Medical TreatmentOther
Also called SMT
Standard medical treatment according to the institution's standard practice
| Study group | Role | What they receive |
|---|---|---|
| SMT + PE-A 5% | Experimental | 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. Receives: Biological: SMT + PE-A 5% |
| SMT Alone | Active comparator | Standard medical treatment (SMT) will be administered according to institution standard practices. Receives: Other: Standard Medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Death Without a Prior Liver Transplant Through Day 90 After Randomization
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)].
Measured: Up to Day 90
Secondary outcomes (2)
Time to Liver Transplant or Death Through Day 90 After Randomization
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)].
Measured: Day 1 to Day 90
Time to Death Without a Prior Liver Transplant Through Day 28 After Randomization
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)].
Measured: Day 1 to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2018
- Study start17 Jun 2019
- Primary completion14 Apr 2025
- Study completion14 Apr 2025
Why it stopped: Due to corporate business reasons only (non-safety related decision)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute-On-Chronic Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 274 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Grifols, S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03702920
- Sponsor's protocol ID
- IG1407
- Acronym
- APACHE
- Status last verified
- May 2026
- First submitted
- 9 Oct 2018
- Last updated
- 4 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03702920
- Acronym / sponsor ID
- APACHE / IG1407
- Conditions
- Acute-On-Chronic Liver Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to corporate business reasons only (non-safety related decision)
- Enrolment
- 274 participants (actual)
- Lead sponsor
- Instituto Grifols, S.A.Industry (pharma, biotech, devices)
- Study start
- 17 Jun 2019 (actual)
- Primary completion
- 14 Apr 2025 (actual)
- Study completion
- 14 Apr 2025 (actual)
- First posted
- 11 Oct 2018 (actual)
- Results
- Posted 4 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SMT + PE-A 5% | Experimental | Biological: 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. |
| SMT Alone | Active comparator | Other: Standard Medical TreatmentStandard medical treatment (SMT) will be administered according to institution standard practices. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SMT + PE-A 5%Also: Albutein 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. | Biological | SMT + PE-A 5% |
| Standard Medical TreatmentAlso: SMTStandard medical treatment according to the institution's standard practice | Other | SMT Alone |
Primary outcome
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)].
2 secondary outcomes
Time to Liver Transplant or Death Through Day 90 After Randomization
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
30 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SMT + PE-A 5% and Standard Medical Treatment in people with Acute-On-Chronic Liver Failure, run by Instituto Grifols, S.A. at 30 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Germany, Italy, Spain, United Kingdom and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Death Without a Prior Liver Transplant Through Day 90 After Randomization (time frame: Up to Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.