TY - JOUR
T1 - Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure
AU - Agarwal, Banwari
AU - Cañizares, Rafael Bañares
AU - Saliba, Faouzi
AU - Ballester, Maria Pilar
AU - Tomescu, Dana Rodica
AU - Martin, Daniel
AU - Stadlbauer, Vanessa
AU - Wright, Gavin
AU - Sheikh, Mohammed
AU - Morgan, Carrie
AU - Alzola, Carlos
AU - Lavin, Phillip
AU - Green, Daniel
AU - Kumar, Rahul
AU - Sacleux, Sophie Caroline
AU - Schilcher, Gernot
AU - Koball, Sebastian
AU - Tudor, Andrada
AU - Minten, Jaak
AU - Domenech, Gema
AU - Aragones, Juan Jose
AU - Oettl, Karl
AU - Paar, Margret
AU - Waterstradt, Katja
AU - Bode-Boger, Stefanie M.
AU - Ibáñez-Samaniego, Luis
AU - Gander, Amir
AU - Ramos, Carolina
AU - Chivu, Alexandru
AU - Stange, Jan
AU - Lamprecht, Georg
AU - Sanchez, Moises
AU - Mookerjee, Rajeshwar P.
AU - Davenport, Andrew
AU - Davies, Nathan
AU - Pavesi, Marco
AU - Andreola, Fausto
AU - Albillos, Agustin
AU - Cordingley, Jeremy
AU - Schmidt, Hartmut
AU - Carbonell-Asins, Juan Antonio
AU - Arroyo, Vicente
AU - Fernandez, Javier
AU - Mitzner, Steffen
AU - Jalan, Rajiv
PY - 2023/5/31
Y1 - 2023/5/31
N2 - 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.
AB - 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.
U2 - 10.1016/j.jhep.2023.03.013
DO - 10.1016/j.jhep.2023.03.013
M3 - Article
SN - 0168-8278
VL - 0
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 0
ER -