Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on-chronic liver failure
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2023
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Elsevier
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Agarwal, Banwari; Rafael Banares Cañizares; Saliba, Faouzi; Ballester, Maria Pilar; Tomescu, Dana Rodica; Martin, Daniel; Stadlbauer, Vanessa; Wright, Gavin; Sheikh, Mohammed; Morgan, Carrie; Alzola, Carlos; Lavin, Phillip; Green, Daniel; Kumar, Rahul; Sacleux, Sophie Caroline; Schilcher, Gernot; Koball, Sebastian; Tudor, Andrada; Minten, Jaak; Domenech, Gema; Aragones, Juan Jose; Oettl, Karl; Paar, Margret; Waterstradt, Katja; Bode-Boger, Stefanie M.; Ibanez-Samaniego, Luis; Gander, Amir; Ramos, Carolina; Chivu, Alexandru; Stange, Jan; Lamprecht, Georg; Sanchez, Moises; Mookerjee, Rajeshwar P.; Davenport, Andrew; Davies, Nathan; Pavesi, Marco; Andreola, Fausto; Albillos, Agustin; Cordingley, Jeremy; Schmidt, Hartmut; Carbonell-Asins, Juan Antonio; Arroyo, Vicente; Fernandez, Javier; Mitzner, Steffen; Jalan, Rajiv. Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on-chronic liver failure. JOURNAL OF HEPATOLOGY 2023; 79: 79-92
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 randomizedcontrolled
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 prespecified
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.
Clinical trial number: NCT03065699.
Description
Se trata de un artículo que describe, por primera vez en humanos, la seguridad y el impacto fisiopatológico de un nuevo dispositivo de soporte hepático artificial, diseñado específicamente para antagonizar los mecanismos fisiopatológicos de la cirrosis descompensada. El estudio , financiado mediante un proyecto europeo, indica que el dispositivo es seguro, aplicable, tiene influencia en los numerosos aspectos mecanísticos explorados y, finalmente, apuntando a datos de posible eficacia clínica. Globalmente, se puede considerar que el estudio es una evidente prueba de concepto positiva. Desde el punto de vista de la trascendencia social y sanitaria, si los estudios en fase III determinan la eficacia sobre variables clínicas, representaría una herramienta de gran valor para el tratamiento de pacientes con cirrosis y con fracaso hepático agudo sobre crónico. La revista Journal of Hepatology está en el primer decil de la especialidad con un FI de XXX. El investigador solicitante del sexenio es primer firmante del artículo habiendo participado en el diseño y ejecución del proyecto así como en la elaboración de los resultados y del manuscrito en todas sus fases. Representa además la continuacion en una línea de investigación con numerosas publicaciones previas (Banares R et al. Hepatology 2013; Saliba F, Bañares R et al. Intensive Care Medicine 2022)