Very Low-volume Plasma Exchange in ACLF

Summary

This is a prospective, multicenter, open-label, non-inferiority, randomized controlled trial evaluating the efficacy and safety of very low plasma exchange (400 mL plasma + prothrombin complex concentrate) and plasma-free (prothrombin complex concentrate only) artificial liver support systems compared with standard low-volume plasma exchange (1000 mL plasma) in patients with acute-on-chronic liver failure (ACLF). A total of 840 eligible patients (COSSH grade 1-2) will be enrolled from 10 centers across China and randomly assigned in a 1:1:1 ratio to receive three sessions of treatment (every 2-3 days) combined with standard medical therapy. The primary endpoint is 28-day non-liver-transplant mortality, with a non-inferiority margin of 10%. Secondary endpoints include 90-day non-liver-transplant mortality, 90-day bridging to liver transplantation rate, changes in prognostic scores (COSSH-ACLF Ⅱ, MELD, CLIF-C ACLFs) from baseline at 2 weeks, and total plasma volume used during hospitalization. Safety outcomes include adverse events (bleeding, coagulation disorders, thrombosis, hypotension, infections, allergic reactions). The study aims to establish a plasma-sparing treatment strategy that reduces dependence on blood products while maintaining non-inferior efficacy. The trial is funded by the National Science and Technology Major Project of China and approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (Approval No.: 中大附三医伦RG2026-044-01; Approval Date: April 29, 2026). Enrollment is planned from May 2026 to October 2027, with follow-up completed by October 2028. Written informed consent will be obtained from all participants.

Timeline

Start

2026-10-01

Primary completion

2028-11-05

Completion

2028-12-05

Publications

• Results Ocskay K, Kanjo A, Gede N, Szakacs Z, Par G, Eross B, Stange J, Mitzner S, Hegyi P, Molnar Z. Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis. Ann Intensive Care. 2021 Jan 18;11(1):10. doi: 10.1186/s13613-020-00795-0.
• Results Saliba F, Banares R, Larsen FS, Wilmer A, Pares A, Mitzner S, Stange J, Fuhrmann V, Gilg S, Hassanein T, Samuel D, Torner J, Jaber S. Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts. Intensive Care Med. 2022 Oct;48(10):1352-1367. doi: 10.1007/s00134-022-06802-1. Epub 2022 Sep 6.
• Results Fernandez J, Acevedo J, Wiest R, Gustot T, Amoros A, Deulofeu C, Reverter E, Martinez J, Saliba F, Jalan R, Welzel T, Pavesi M, Hernandez-Tejero M, Gines P, Arroyo V; European Foundation for the Study of Chronic Liver Failure. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut. 2018 Oct;67(10):1870-1880. doi: 10.1136/gutjnl-2017-314240. Epub 2017 Aug 28.

Drugs

Indications