Clinical Studies

International registry on the use of the CytoSorb(R) adsorber in ICU patients : Study protocol and preliminary results.

Friesecke S, Trager K, Schitter GA, Molnar Z, Bach F, Kogelmann K, Bogdanski R, Weyland A, Nierhaus A, Nestler F, Olboeter D, Tomescu D, Jacob D, Haake H, Grigorjev E, Nitsch M, Baumann A, Quintet M, Schott M, Kielstein JT, Meier-Hellmann A, Born F, Schumacher U, Singer M, Kellum J, Brunkhorst FM.
Med Klin Intensivmed Notfallmed 2017; epub

This is the third interim analysis from the CytoSorb clinical registry where the aim is...

This is the third interim analysis from the CytoSorb clinical registry where the aim is to record the use of CytoSorb adsorbers in critically ill patients under real-life conditions. It records all relevant information in the course of product use, including diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 +/- 15.1 years). In all, 192 (97.0%) had 1 to 5 Cytosorb(R) adsorber applications. Sepsis was the most common indication for CytoSorb(R) treatment (135 patients). Mean APACHE II score in this group was 33.1 +/- 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment, however interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. Patient numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as a potentially beneficial treatment in life-threatening situations. Treating physicians rated the condition of the patients as much or very much improved in approximately 50% of cases and reported a very favorable safety profile with no device-associated side effects.

Extracorporeal Cytokine Elimination as Rescue Therapy in Refractory Septic Shock – a Prospective Single-Center Study

Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A
Journal Artif Organs 2017; pub

Mortality from refractory septic shock may reach 90-100% despite optimum therapy. In this study extracorporeal...

Mortality from refractory septic shock may reach 90-100% despite optimum therapy. In this study extracorporeal cytokine adsorption using CytoSorb in addition to regular therapy was studied prospectively in 20 patients with refractory shock (defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for six hours). CytoSorb® treatment was started after 7.8 ± 3.7 hours of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (p=0.03) and 12 hours (p=0.001). Lactate clearance improved significantly. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45% (predicted mortality from the SOFA score was >80%). The use of CytoSorb adsorption therapy resulted in shock reversal in two thirds of these particularly difficult to treat patients.

Use of cytokine filters in cardiopulmonary bypass machines. (Einsatz eines Zytokinfilters in die Herz-Lungen-Maschine)

Deppe AC, Weber C, Choi YH, Wahlers T.
Z Herz- Thorax-Gefäßchir 2016 30(4): 254-259

Abstract and article in German, abstract only in English.

Cardiac surgical interventions using a...

Abstract and article in German, abstract only in English.

Cardiac surgical interventions using a cardiopulmonary bypass (CPB) machine induce a systemic inflammatory reaction due to activation of multiple inflammatory cascades. In the postoperative phase this can result in systemic inflammatory response syndrome (SIRS). Activation of various mediators of inflammation, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) can lead to postoperative complications, organ dysfunction, morbidity and mortality. The effect of adsorption of cytokines using CytoSorb® with a CPB machine during cardiac surgery is evaluated. The study is being conducted as a prospective, observational pilot study to determine the clinical impact of the use of an adsorption filter (CytoSorb®) on the serum levels of IL-6, IL-8 and TNF-alpha using a CPB machine. This pilot study includes 300 patients planned for elective surgical myocardial revascularization, partitioned into 3 groups each with 100 patients with on-pump myocardial revascularization
with CytoSorb®, on-pump myocardial revascularization without CytoSorb® and off- pump myocardial revascularization. Primary outcome measures are the inflammatory response serum parameters IL-6, IL-8, TNF- alpha, complement C3/C4, leucocyte counts and C-reactive protein. Secondary outcome measures are length of intensive care unit (ICU) and total hospital stay, duration of ventilation, duration of catecholamine therapy, kidney injury as well as major adverse cardiac and cerebrovascular events. Interim analysis after concluding 60 % of the planned patients revealed a well- balanced group allocation of patients. In the group with CytoSorb® the IL-6 values are decreased, whereas TNF-alpha values are comparable between the three groups. There was reduced sternal wound infections and lower usage of antibiotics in the CytoSorb group. The use of the CytoSorb® filter during CPB is safe compared with the standard procedure and applicable without technical difficulties. CytoSorb® reduces the cytokine load and seems to attenuate the inflammatory response.

Effect of hemoadsorption during cardiopulmonary bypass surgery – a blinded, randomized, controlled pilot study using a novel adsorbent.

Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, Lamm C, Preißing F, Wiedemann D, Hiesmayr MJ, Spittler A
Crit Care. 2016 Apr 9;20(1):96.

Objective of this first blinded, randomized and controlled single-center trial in 46 adult patients undergoing...

Objective of this first blinded, randomized and controlled single-center trial in 46 adult patients undergoing elective open heart surgery (coronary artery bypass graft [CABG], valve surgery, combined procedure) with an expected CPB duration of more than 120 min was to test CytoSorb installed in the cardiopulmonary bypass (CPB) circuit (intraoperative usage) on changes of pro- and anti-inflammatory cytokines levels, inflammation markers, and differences in patients’ perioperative course. The authors did not find any reduction of the pro-inflammatory response in patients and therefore no changes in their perioperative course. Of note, only the least sick cohort of patients undergoing relatively low-risk cardiac surgery were included in this study. Therefore the observed inflammatory response was only moderate also in the control group. The use and installation of the CytoSorbadsorber in a CPB circuit were technically feasible, and no adverse device-related side effects occurred. The results also show that albumin and platelet levels are not significantly affected by CytoSorb. There is a possible protective effect of the observed elevated IL- 10 levels postoperatively, which have been associated with lower mortality in previous studies. After safety and feasibility have been demonstrated, patient groups with the best clinical benefit from CytoSorb need to be identified.

RECCAS – REmoval of Cytokines during CArdiac Surgery: study protocol for a randomised controlled trial.

Baumann A, Buchwald D, Annecke T, Hellmich M, Zahn PK, Hohn A
Trials. 2016 Mar 12;17(1):137

On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction...

On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction associated with poor clinical outcome and CytoSorb promises to attenuate this inflammatory response. Aim of the single-centrerandomised, two-arm, patient- blinded RECCAS trial is to assess the efficacy of intraoperative CytoSorb usage during cardiopulmonary bypass (CPB) to reduce the proinflammatory cytokine (i.e. IL-6) burden during and after on-pump cardiac surgery as well as to evaluate the effects on postoperative organ dysfunction and outcomes in patients at high risk. Differences in secondary outcome variables between the study groups may give rise to further studies and may lead to a better understanding of the mechanisms of CytoSorb treatment

International registry on the use of the CytoSorb-Adsorber in ICU patients (NCT02312024)

Schein M, Bahr V, Rissner F, Jakob M, Schumacher U, Brunkhorst FM
Infection. 2015 Aug;43Suppl 1:1-73. Abstract No. 125

This article gives an overview on the objectives and methods of the currently implemented international...

This article gives an overview on the objectives and methods of the currently implemented international CytoSorb registry.

Feasibility study of cytokine removal by hemoadsorption in brain-dead humans

Kellum JA, Venkataraman R, Powner D, Elder M, Hergenroeder G, Carter M
Crit Care Med. 2008 Jan;36(1):268-72

Through numerousmechanisms, brain death is associatedwith a massive release of proinflammatory cytokines, detectable both in...

Through numerousmechanisms, brain death is associatedwith a massive release of proinflammatory cytokines, detectable both in blood and transplantable organs. This increased inflammatory response has been associated withpoor allograft function before and after transplantation. Therefore, this in vivo study examines the feasibility of hemoadsorption (using CytoSorb) to remove cytokines in brain-dead humans (n=8).