NCT03702920

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

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

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 275 (actual)
• Sponsor: Grifols Therapeutics LLC · Industry
• Sex: All
• Age: 18 Years – 79 Years
• Healthy volunteers: Not accepted

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.

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. 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: The Treatment Period will be 7 days for all subjects and will be prolonged depending on subject's ACLF evolution to up to 17 days. 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

Interventions

Type	Name	Description
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.
OTHER	Standard Medical Treatment	Standard medical treatment according to the institution's standard practice

Timeline

• Start date: 2019-02-21
• Primary completion: 2025-04-14
• Completion: 2025-04-14
• First posted: 2018-10-11
• Last updated: 2025-12-16

Locations

40 sites across 10 countries: United States, Austria, Belgium, Denmark, France, Germany, Italy, Portugal, Spain, United Kingdom

Regulatory

• FDA-regulated drug study