Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Banwari Agarwal, Rafael Bañares Cañizares, Faouzi Saliba, Maria Pilar Ballester, Dana Rodica Tomescu, Daniel Martin, Vanessa Stadlbauer, Gavin Wright, Mohammed Sheikh, Carrie Morgan, Carlos Alzola, Phillip Lavin, Daniel Green, Rahul Kumar, Sophie Caroline Sacleux, Gernot Schilcher, Sebastian Koball, Andrada Tudor, Jaak Minten, Gema DomenechJuan Jose Aragones, Karl Oettl, Margret Paar, Katja Waterstradt, Stefanie M. Bode-Boger, Luis Ibáñez-Samaniego, Amir Gander, Carolina Ramos, Alexandru Chivu, Jan Stange, Georg Lamprecht, Moises Sanchez, Rajeshwar P. Mookerjee, Andrew Davenport, Nathan Davies, Marco Pavesi, Fausto Andreola, Agustin Albillos, Jeremy Cordingley, Hartmut Schmidt, Juan Antonio Carbonell-Asins, Vicente Arroyo, Javier Fernandez, Steffen Mitzner, Rajiv Jalan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background & Aims Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Methods Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). Results There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. Conclusions These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. Impact and implications This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. Clinical trial number NCT03065699.
Original languageEnglish
Number of pages0
JournalJournal of Hepatology
Volume0
Issue number0
Early online date31 May 2023
DOIs
Publication statusPublished - 31 May 2023

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