Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP)-a single center, open-label, three-arm, randomized, controlled intervention trial

Asieb Sekandarzad, Enya Weber, Eric Peter Prager, Erika Graf, Dominik Bettinger, Tobias Wengenmayer, Alexander Supady, Asieb Sekandarzad, Enya Weber, Eric Peter Prager, Erika Graf, Dominik Bettinger, Tobias Wengenmayer, Alexander Supady

Abstract

Background: Liver cirrhosis is a major healthcare problem and the mortality rate is high. During recent years, systemic inflammation has been recognized as a major driver of hepatic decompensation and progression of liver cirrhosis to acute-on-chronic liver failure (ACLF). The aim of the CYTOHEP study is to assess the impact of extracorporeal hemoadsorption with the CytoSorb adsorber on serum bilirubin concentrations, humoral inflammation parameters, liver function parameters, and patient survival in patients with ACLF and acute kidney injury (AKI).

Methods: The CYTOHEP study is a prospective, single-center, open-label, three-arm, randomized, controlled intervention trial. Patients with ACLF and AKI stage 3 according to Kidney Disease: Improving Global Outcome (KDIGO) criteria will be randomized into three groups to be treated with (1) continuous renal replacement therapy (CRRT) and CytoSorb, (2) CRRT without CytoSorb, and (3) without both, CRRT and CytoSorb. In the hemoadsorption group, CytoSorb will be used for 72 h. The other groups receive standard of care with early or late initiation of CRRT, respectively. Primary endpoint of the study is serum bilirubin concentration after 72 h, important secondary endpoints are 30-day survival and a panel of inflammatory parameters.

Discussion: The CYTOHEP study is designed to evaluate the benefit of extracorporeal hemoadsorption in patients with ACLF. The results of this study will help to better understand the potential role of hemoadsorption for the treatment of ACLF and its impact on bilirubin levels, inflammatory parameters, and survival.

Trial registration: ClinicalTrials.gov NCT05019352. Registered on August 24, 2021. Deutsches Register Klinischer Studien (DRKS) DRKS00026082.

Keywords: Acute-on-chronic liver failure; CytoSorb; Extracorporeal hemoadsorption; Liver cirrhosis; Randomized controlled trial.

Conflict of interest statement

ASu received speakers’ honoraria from CytoSorbents, the manufacturer of the CytoSorb device. ASu also received an unrestricted research grant from CytoSorbents. DB received speakers’ honoraria from Bayer Healthcare and the Falk Foundation. Further, he receives consulting honoraria from Bayer Healthcare, Boston Scientific, and Shionogi. EP received consulting honoraria from Novartis Pharma.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Graphical representation of the study design
Fig. 2
Fig. 2
Schematic structure of the incorporation of the CytoSorb Adsorber into the CRRT system, blood flow in the direction of the arrows in red [source: https://cytosorb-therapy.com/de/der-adsorber/setup-von-cytosorb/]
Fig. 3
Fig. 3
Participant timeline displaying timepoints of interventions and assessments during the 30-day study period. After the end of study (day 30) survival of the study participants will be followed up until day 90. CS, CytoSorb

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