Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial

Alexander Supady; Enya Weber; Marina Rieder; Achim Lother; Tim Niklaus; Timm Zahn; Franziska Frech; Sissi Müller; Moritz Kuhl; Christoph Benk; Sven Maier; Georg Trummer; Annabelle Flügler; Kirsten Krüger; Asieb Sekandarzad; Peter Stachon; Viviane Zotzmann; Christoph Bode; Paul M Biever; Dawid Staudacher; Tobias Wengenmayer; Erika Graf; Daniel Duerschmied

doi:10.1016/S2213-2600(21)00177-6

Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial

Lancet Respir Med. 2021 Jul;9(7):755-762. doi: 10.1016/S2213-2600(21)00177-6. Epub 2021 May 14.

Authors

Alexander Supady¹, Enya Weber², Marina Rieder³, Achim Lother³, Tim Niklaus³, Timm Zahn³, Franziska Frech³, Sissi Müller³, Moritz Kuhl³, Christoph Benk⁴, Sven Maier⁴, Georg Trummer⁴, Annabelle Flügler³, Kirsten Krüger³, Asieb Sekandarzad³, Peter Stachon³, Viviane Zotzmann³, Christoph Bode³, Paul M Biever³, Dawid Staudacher³, Tobias Wengenmayer³, Erika Graf⁵, Daniel Duerschmied³

Affiliations

¹ Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Germany; Heidelberg Institute of Global Health, University of Heidelberg, Germany. Electronic address: alexander.supady@uniklinik-freiburg.de.
² Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Medical Center, Faculty of Medicine, University of Freiburg, Germany.
³ Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Germany.
⁴ Department of Cardiovascular Surgery, Heart Center, Faculty of Medicine, University of Freiburg, Germany.
⁵ Institute of Medical Biometry and Statistics, Faculty of Medicine, University of Freiburg, Germany; Medical Center, Faculty of Medicine, University of Freiburg, Germany.

Abstract

Background: We sought to clarify the benefit of cytokine adsorption in patients with COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO).

Methods: We did a single-centre, open-label, randomised, controlled trial to investigate cytokine adsorption in adult patients with severe COVID-19 pneumonia requiring ECMO. Patients with COVID-19 selected for ECMO at the Freiburg University Medical Center (Freiburg, Germany) were randomly assigned (1:1) to receive cytokine adsorption using the CytoSorb device or not. Randomisation was computer-generated, allocation was concealed by opaque, sequentially numbered sealed envelopes. The CytoSorb device was incorporated into the ECMO circuit before connection to the patient circuit, replaced every 24 h, and removed after 72 h. The primary endpoint was serum interleukin-6 (IL-6) concentration 72 h after initiation of ECMO analysed by intention to treat. Secondary endpoints included 30-day survival. The trial is registered with ClinicalTrials.gov (NCT04324528) and the German Clinical Trials Register (DRKS00021300) and is closed.

Findings: From March 29, 2020, to Dec 29, 2020, of 34 patients assessed for eligibility, 17 (50%) were treated with cytokine adsorption and 17 (50%) without. Median IL-6 decreased from 357·0 pg/mL to 98·6 pg/mL in patients randomly assigned to cytokine adsorption and from 289·0 pg/mL to 112·0 pg/mL in the control group after 72 h. One patient in each group died before 72 h. Adjusted mean log IL-6 concentrations after 72 h were 0·30 higher in the cytokine adsorption group (95% CI -0·70 to 1·30, p=0·54). Survival after 30 days was three (18%) of 17 with cytokine adsorption and 13 (76%) of 17 without cytokine adsorption (p=0·0016).

Interpretation: Early initiation of cytokine adsorption in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6 and had a negative effect on survival. Cytokine adsorption should not be used during the first days of ECMO support in COVID-19.

Funding: None.

Publication types

Randomized Controlled Trial

MeSH terms

Adsorption
Adult
Aged
COVID-19 / therapy*
Cytokines*
Extracorporeal Membrane Oxygenation*
Female
Humans
Male
Middle Aged

Substances

Cytokines

Associated data

ClinicalTrials.gov/NCT04324528