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

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.

Cytokine adsorption and ECMO in patients with COVID-19 – Author's reply

“…We thank Andrey Rybalko, Pasquale Nardelli, and their colleagues for critically discussing the results from our CYCOV trial 1 and raising valid points.…”

“…During the CYCOV trial, 1 four different ECMO systems and three different cannulation strategies were used ( table ). The secondary endpoint, number of days on ECMO, was reported in the appendix of the Article.…”

Cytokine adsorption and ECMO in patients with COVID-19

“…As a cytokine storm was proposed among pathogenetic mechanisms of severe COVID-19, interest in control of cytokines increased dramatically during the pandemic. Therefore, the trial by Alexander Supady and colleagues 1 is timely and offers interesting insights, but their findings must be carefully discussed before conclusions can be applied to clinical practice.…”

Cytokine adsorption and ECMO in patients with COVID-19

“…We read with interest the CYCOV trial by Alexander Supady and colleagues, 1 in which the authors describe extracorporeal membrane oxygenation (ECMO) support in patients with severe COVID-19 combined with cytokine adsorption. The authors conclude that cytokine adsorption during the first 72 h of ECMO support did not result in reduced interleukin (IL)-6 concentrations after 72 h, that cytokine adsorption was associated with an increased mortality risk within 30 days after initiation of ECMO, and that early cytokine adsorption should be avoided in patients with COVID-19 requiring venovenous ECMO support.…”