Adjuvant Therapy With CytoSorb in Refractory Septic Shock (ACYSS)

Effect of the CytoSorb Adsorber on Hemodynamic, Immunological and Pharmacokinetic Parameters in Refractory Septic Shock

This prospective randomized single center study investigates to what extent the removal of elevated cytokine levels by hemoadsorption has a positive effect on the treatment of patients in septic shock by stabilizing the circulatory situation.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Device: CytoSorb-Therapy

Detailed Description

The term "sepsis" refers to a clinical syndrome in which a dysregulation of the host's inflammatory reaction to infection leads to a life-threatening of organ dysfunctions. Sepsis and septic shock are major causes of death in intensive care units worldwide.

The clinical picture of septic shock, the most severe form of sepsis, leads to uncontrolled production and release of a large number of proinflammatory cytokines and mediators, the "cytokine storm". Septic shock is accompanied by a massive increase in mortality of up to 60%.

This high mortality rate is due to a lack of current treatment options. The early recognition of the disease and its immediate treatment are decisive for successful therapy and the survival of those affected. The most important therapeutic steps, apart from focus control by antibiotics and surgical intervention, are the stabilization of the affected organ systems, in particular the circulatory system and the respiratory system. As an extracorporeal and non-specific procedure for the interruption of the cytokine storm, hemoadsorption by means of CytoSorb adsorbers may be an intervention, which has already demonstrated its basic effectiveness in the treatment of septic and cardiosurgical patients.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominik Jarczak, MD; Phone Number: +49 40 741035315; Email: d.jarczak@uke.de
• Study Contact Backup: Name: Axel Nierhaus, MD; Phone Number: +49 40 741035315; Email: nierhaus@uke.de

Study Locations

• Germany
  • Hamburg, Germany
    • Recruiting
    • University Medical Center Hamburg-Eppendorf
    • Contact: Dominik Jarczak, MD; Phone Number: +49 40 741035315; Email: d.jarczak@uke.de
    • Contact: Axel Nierhaus, MD; Phone Number: +49 40 741035315; Email: nierhaus@uke.de
    • Principal Investigator: Stefan Kluge, MD
    • Sub-Investigator: Dominik Jarczak, MD
    • Sub-Investigator: Axel Nierhaus, MD
    • Sub-Investigator: Christina König, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Refractory septic shock
• Need for Norepinephrine ≥ 0.25 µg/kg/min
• IL6 ≥ 1000 ng/l
• Indication for CRRT

Exclusion Criteria:

• Sepsis due to pulmonary or urogenital causes
• Onset of septic shock longer than 36 hours
• Liver cirrhosis Child Pugh C
• "do not resuscitate"-order
• expected survival < 14 days
• participation in another interventional trial
• Pregnancy or breastfeeding
• Lack of consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CytoSorb-Therapy; Therapy of septic shock using guideline directed standard of care, including continuous renal replacement therapy in combination with haemadsorption using CytoSorb-Adsorber	Device: CytoSorb-Therapy; Additional use of Cytosorb-Adsorber in patients with septic shock and need for continuous renal replacement therapy
No Intervention: Standard of care; Therapy of septic shock using guideline directed standard of care, including continuous renal replacement therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 48 hours of treatment	Percentage of patients with a reduction of catecholamine dose of at least 25% compared to baseline for at least 6 hours within the first 48 hours of treatment.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in organ dysfunction	Change in organ dysfunction based on "Sequential Organ Failure Assessment" (SOFA) Score The SOFA score is made of 6 variables, each representing an organ system. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure) The worst physiological variables were collected serially every 24 hours of a patient's ICU admission. The "worst" measurement was defined as the measure that correlated to the highest number of points. The SOFA score ranges from 0 to 24.	10 days
Lactate clearance	Improving lactate clearance by lowering serum lactate levels	10 days
Renal replacement therapy	Time with need for renal replacement therapy	10 days
Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 24 hours of treatment	Percentage of patients with a reduction of catecholamine dose of at least 25% compared to baseline for at least 6 hours within the first 48 hours of treatment.	24 hours
End of septic shock	Time until shock resolution	10 days
ICU length of stay	ICU length of stay	90 days
Time on mechanical ventilation	Time on mechanical ventilation	10 days
Cumulative catecholamine dose	Cumulative catecholamine dose	10 days
Overall and ICU mortality	Overall and ICU mortality	90 days
Serum levels of administered anti-infectives	Serum drug Levels of pre and post filter and adsorber system on day 1-3 while CytoSorb therapy (sampling: t 0, 1, 2, 6, 8, 12, 24 h after CytoSorb initiation)	3 days
Change of plasma Interleukin-6 (IL6) level	Change of plasma Interleukin-6 (IL6) level	10 days
Change of plasma Interleukin-10 (IL10) level	Change of plasma Interleukin-10 (IL10) level	10 days
Change of plasma Procalcitonin (PCT) level	Change of plasma Procalcitonin (PCT) level	10 days
Change of HLA-DR level	Change of HLA-DR (Human Leukocyte Antigen - DR isotype) level of monocytes	10 days
Change of TNF alpha level after ex-vivo stimulation	Change of TNF-alfa level (Tumor Necrosis Factor alpha) level after LPS (Lipopolysaccharides) stimulation as sign of monocytic immunocompetence	10 days

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: CytoSorbents, Inc
• Investigators: Principal Investigator: Stefan Kluge, MD, University Hospital Hamburg-Eppendorf, Department of Intensive Care Medicine

Publications and helpful links

General Publications

• Taeb AM, Hooper MH, Marik PE. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management. Nutr Clin Pract. 2017 Jun;32(3):296-308. doi: 10.1177/0884533617695243. Epub 2017 Mar 17.
• Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs. 2017 Sep;20(3):252-259. doi: 10.1007/s10047-017-0967-4. Epub 2017 Jun 6.
• Garau I, Marz A, Sehner S, Reuter DA, Reichenspurner H, Zollner C, Kubitz JC. Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor alpha serum levels in cardiac surgery: a randomized controlled trial. Minerva Anestesiol. 2019 Jul;85(7):715-723. doi: 10.23736/S0375-9393.18.12898-7. Epub 2018 Nov 22.
• Kogelmann K, Jarczak D, Scheller M, Druner M. Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care. 2017 Mar 27;21(1):74. doi: 10.1186/s13054-017-1662-9.
• Bayer O, Reinhart K, Kohl M, Kabisch B, Marshall J, Sakr Y, Bauer M, Hartog C, Schwarzkopf D, Riedemann N. Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal, fluid balance, and patient outcomes in patients with severe sepsis: a prospective sequential analysis. Crit Care Med. 2012 Sep;40(9):2543-51. doi: 10.1097/CCM.0b013e318258fee7.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 15, 2019
• First Submitted That Met QC Criteria: July 7, 2019
• First Posted (Actual): July 9, 2019

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 6, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Sepsis; Pharmacokinetic; CytoSorb; Critically ill; Intensive care medicine; Hemoadsorption
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: ACYSS; DRKS00015483 (Registry Identifier: Deutsches Register Klinischer Studien)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No