Cytosorb® Rescue for COVID-19 Patients with Vasoplegic Shock (CytoResc): A Prospective, Open-Label, Randomised Controlled Pilot Study

Background: Several observations indicate a hyperinflammatory state in severely ill COVID-19 patients. The aim of this study was to investigate the effect of extracorporeal cytokine elimination by CytoSorb® on COVID-19 associated vasoplegic shock. Methods: In this prospective randomised pilot study COVID-19 patients with vasoplegic shock requiring norepinephrine >0·2 µg/kg/min, CRP >100 mg/L and indication for hemodialysis were randomised 1:1 to receive CytoSorb® treatment for 3-7 days or standard of care. The primary endpoint was time until resolution of vasoplegic shock, estimated by a Cox-regression model. Secondary endpoints included mortality, serum interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). Findings: From November 2020 to March 2021, 50 patients were enrolled of which 23 patients were randomised to receive CytoSorb® treatment and 26 patients to receive standard of care. One patient randomised to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 (56·5%) of 23 patients in the CytoSorb® and 12 (46·2%) of 26 patients in the control group after a median of 5 (IQR 4-5) and 4 (IQR 3-5) days, respectively. The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, ECMO-therapy, or time from shock onset to study inclusion was HR 1·23 (95%CI: 0·54-2·79), p=0·63). The mortality rate was 78% in the CytoSorb® and 73% in the control group (unadjusted HR 1·17 (95%CI: 0·61-2.23), p=0·64). The effects on inflammatory markers and catecholamine requirements and the type and rates of adverse events were similar in the two groups. Interpretation: In this pilot trial in severely ill COVID-19 patients CytoSorb® treatment did not improve resolution of vasoplegic shock as compared to standard treatment. Mortality rates, catecholamine requirements, inflammatory markers and adverse events did not differ between the two groups. Trial Registration: The study was registered in the German Registry of Clinical Trials (DRKS00021447 Funding: Internal university funds Declaration of Interest: HS, LJL, MP, TK, PT, FS, KUE, SK, JVK, MO, AKru, A Kra, KB declare no conflicts of interest. PE received honoraria from GSK and AstraZeneca and filed two patents for novel urinary biomarkers outside the submitted work. ST received research funding and honoraria for workshops and lectures from Orionpharma. He additionally received honoraria for workshops and lectures from Edwards and honoraria for lectures from Amomed and SmithN German Reseach Society; German Aerospace Center; Einstein Foundation Berlin; Federal Joint Committee (G-BA); Inner University grants; Project Management Agency; Non-Profit Promoting Science and Education; European Society of Anesthesiology and Intensive Care; Baxter Deutschland GmbH; Cytosorbents Europe GmbH; Edwards Lifsciences Germany GmbH; Fresenius Medical Care; Grunenthal GmbH; Massimo Europe Ltd.; Pfizer Pharma PFE GmbH; Georg Thieme Verlag, Dr. F Kohler Chemie GmbH; Sintetica GmbH; Stifterverband fur die deutsche Wissenschaft e.V./Philips; Stiftung Charie; AGUETTANT Deutschland GmbH; AbbVie Deutschland GmbH & Co.KG; Amomed Pharma GmbH; InTouch Health; Copra System GmbH; Correvio GmbH; Max Plank Gesellschaft zur Forderung der Wissenschaften e.V.; Deutsche Gesellschaft fur Anasthesiologie & Intensivmedizin (DGAI); Stifterverband fur die Deutsche Wissenschaft e.V./Medtronic; Philipps ElectronicsNederland BV; BMG, BMBF, German Research Society all outside the submitted work. In addition, CS has different patents. DK received fees for speaking at a symposia organized on behalf of Fresenius Medical Care AG, Germany. Ethical Approval: The original protocol and the changes were approved by the local ethics committee (EA1/069/20).