Trial Outcomes & Findings for Short-term Survival of Subjects With Acute-on-chronic Liver Failure After Plasma Exchange With Human Serum Albumin 5% (NCT NCT03702920)

Last Updated: 2026-06-04

Results Overview

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 \[(participants with an event up to the analysis cut-off day) / (number of participants in the ITT group)\].

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

274 participants

Primary outcome timeframe

Up to Day 90

Results posted on

2026-06-04

Participant Flow

A total of 274 participants took part in the study at 29 investigative sites across 8 countries in Europe and the United States from 17 June 2019 to 14 April 2025.

318 participants with ACLF were screened of which 274 participants were randomized in a 1:1 ratio to receive either the Standard Medical Treatment (SMT) + PE-A 5% or the SMT Alone.

Participant milestones

Participant milestones
Measure	SMT + PE-A 5% PE-A 5% was performed using 5% albumin and FFP as replacement fluids. FFP was administered after the 5% albumin administration to prevent coagulopathy, and the PE-A 5% session was to be considered completed at the end of the FFP administration. The amount of Albutein 5% and FFP to be infused was determined by the INR. IVIG was administered intravenously after every 2 PE A 5% sessions in order to prevent the development of hypogammaglobulinemia and infection. Standard medical treatment (SMT) in addition to PE-A 5% was administered per institution standard practices.	SMT Alone Standard medical treatment (SMT) was administered per institution standard practices.
Overall Study STARTED	135	139
Overall Study COMPLETED	36	29
Overall Study NOT COMPLETED	99	110

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Intent-to-treat (ITT) population included all participants who were randomized.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to Day 90

Population: ITT population included all participants who were randomized.

Outcome measures

Outcome measures
Measure	SMT + PE-A 5% n=135 Participants PE-A 5% was performed using 5% albumin and FFP as replacement fluids. FFP was administered after the 5% albumin administration to prevent coagulopathy, and the PE-A 5% session was to be considered completed at the end of the FFP administration. The amount of Albutein 5% and FFP to be infused was determined by the INR. IVIG was administered intravenously after every 2 PE A 5% sessions in order to prevent the development of hypogammaglobulinemia and infection.	SMT Alone n=139 Participants Standard medical treatment (SMT) was administered per institution standards.
Time to Death Without a Prior Liver Transplant Through Day 90 After Randomization	51 Participants	69 Participants

SECONDARY outcome

Timeframe: Day 1 to Day 90

Population: ITT population included all participants who were randomized.

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 \[(participants with an event up to the analysis cut-off day) / (number of participants in the ITT group)\].

Outcome measures

Outcome measures
Measure	SMT + PE-A 5% n=135 Participants PE-A 5% was performed using 5% albumin and FFP as replacement fluids. FFP was administered after the 5% albumin administration to prevent coagulopathy, and the PE-A 5% session was to be considered completed at the end of the FFP administration. The amount of Albutein 5% and FFP to be infused was determined by the INR. IVIG was administered intravenously after every 2 PE A 5% sessions in order to prevent the development of hypogammaglobulinemia and infection.	SMT Alone n=139 Participants Standard medical treatment (SMT) was administered per institution standards.
Time to Liver Transplant or Death Through Day 90 After Randomization	87 Participants	89 Participants

SECONDARY outcome

Timeframe: Day 1 to Day 28

Population: ITT population included all participants who were randomized.

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 \[(participants with an event up to the analysis cut-off day) / (number of participants in the ITT group)\].

Outcome measures

Outcome measures
Measure	SMT + PE-A 5% n=135 Participants PE-A 5% was performed using 5% albumin and FFP as replacement fluids. FFP was administered after the 5% albumin administration to prevent coagulopathy, and the PE-A 5% session was to be considered completed at the end of the FFP administration. The amount of Albutein 5% and FFP to be infused was determined by the INR. IVIG was administered intravenously after every 2 PE A 5% sessions in order to prevent the development of hypogammaglobulinemia and infection.	SMT Alone n=139 Participants Standard medical treatment (SMT) was administered per institution standards.
Time to Death Without a Prior Liver Transplant Through Day 28 After Randomization	39 Participants	51 Participants

Adverse Events

SMT Alone

Serious events: 28 serious events

Other events: 58 other events

Deaths: 70 deaths

SMT + PE-A 5%

Serious events: 37 serious events

Other events: 79 other events

Deaths: 51 deaths

Serious adverse events

Other adverse events

Additional Information

Mireia Torres

Instituto Grifols, S.A.

Phone: +34 93 5710500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Site may publish results from the Study, after providing Sponsor 30 days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to 60 days to allow Sponsor to protect its interests in any Sponsor Inventions.
Publication restrictions are in place

Restriction type: OTHER

Measure	SMT + PE-A 5% n=135 Participants PE-A 5% was performed using 5% albumin and FFP as replacement fluids. FFP was administered after the 5% albumin administration to prevent coagulopathy, and the PE-A 5% session was to be considered completed at the end of the FFP administration. The amount of Albutein 5% and FFP to be infused was determined by the INR. IVIG was administered intravenously after every 2 PE A 5% sessions in order to prevent the development of hypogammaglobulinemia and infection. Standard medical treatment (SMT) in addition to PE-A 5% was administered per institution standard practices.	SMT Alone n=139 Participants Standard medical treatment (SMT) was administered per institution standard practices.	Total n=274 Participants Total of all reporting groups
Race (NIH/OMB) Asian	0 Participants n=9 Participants	4 Participants n=27 Participants	4 Participants n=267 Participants
Age, Continuous	50.3 years STANDARD_DEVIATION 10.92 • n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	51.1 years STANDARD_DEVIATION 11.40 • n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	50.7 years STANDARD_DEVIATION 11.15 • n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Sex: Female, Male Female	46 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	42 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	88 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Sex: Female, Male Male	89 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	97 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	186 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=9 Participants	0 Participants n=27 Participants	1 Participants n=267 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Race (NIH/OMB) Black or African American	7 Participants n=9 Participants	12 Participants n=27 Participants	19 Participants n=267 Participants
Race (NIH/OMB) White	121 Participants n=9 Participants	118 Participants n=27 Participants	239 Participants n=267 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=9 Participants	5 Participants n=27 Participants	11 Participants n=267 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	17 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	31 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	122 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	243 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	0 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	0 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment United States	49 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	48 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	97 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment Austria	7 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	7 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	14 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment Belgium	17 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	17 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	34 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment France	6 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	5 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	11 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment Germany	17 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	14 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	31 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment Italy	15 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	16 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	31 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment Portugal	3 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	2 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	5 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment Spain	16 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	21 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	37 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.
Region of Enrollment United Kingdom	5 Participants n=9 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	9 Participants n=27 Participants • Intent-to-treat (ITT) population included all participants who were randomized.	14 Participants n=267 Participants • Intent-to-treat (ITT) population included all participants who were randomized.

Measure	SMT Alone n=139 participants at risk Standard medical treatment (SMT) was administered per institution standards.	SMT + PE-A 5% n=128 participants at risk PE-A 5% was performed using 5% albumin and FFP as replacement fluids. FFP was administered after the 5% albumin administration to prevent coagulopathy, and the PE-A 5% session was to be considered completed at the end of the FFP administration. The amount of Albutein 5% and FFP to be infused was determined by the INR. IVIG was administered intravenously after every 2 PE A 5% sessions in order to prevent the development of hypogammaglobulinemia and infection.
Metabolism and nutrition disorders Hypokalaemia	15.1% 21/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	14.1% 18/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	5.8% 8/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	6.2% 8/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Metabolism and nutrition disorders Hyperglycaemia	4.3% 6/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	6.2% 8/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Metabolism and nutrition disorders Hypophosphataemia	3.6% 5/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	6.2% 8/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Blood and lymphatic system disorders Anaemia	7.9% 11/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	14.1% 18/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
General disorders Oedema peripheral	3.6% 5/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	9.4% 12/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
General disorders Pyrexia	1.4% 2/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	5.5% 7/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Gastrointestinal disorders Diarrhoea	4.3% 6/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	8.6% 11/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Gastrointestinal disorders Abdominal pain	4.3% 6/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	5.5% 7/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Gastrointestinal disorders Nausea	5.0% 7/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	2.3% 3/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Infections and infestations Urinary tract infection	4.3% 6/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	10.2% 13/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Infections and infestations Pneumonia	7.2% 10/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	2.3% 3/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Vascular disorders Hypotension	7.2% 10/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	10.9% 14/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Cardiac disorders Atrial fibrillation	2.2% 3/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	5.5% 7/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.
Psychiatric disorders Insomnia	1.4% 2/139 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.	5.5% 7/128 • Up to Day 90 Deaths were assessed for the ITT population including all randomized participants. Adverse Events were assessed for the Safety Set which included all randomized participants in the SMT Alone group and participants in the PE-A 5% Arm that received at least one study treatment.