Adjuvant Therapy With CytoSorb in Refractory Septic Shock (ACYSS)

• ClinicalTrials.gov Identifier: NCT04013269
• Recruitment Status: Recruiting
• First Posted: July 9, 2019
• Last Update Posted: November 8, 2022
• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborator: CytoSorbents, Inc
• Information provided by (Responsible Party): Universitätsklinikum Hamburg-Eppendorf

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Septic Shock	Device: CytoSorb-Therapy	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of the CytoSorb Adsorber on Hemodynamic, Immunological and Pharmacokinetic Parameters in Refractory Septic Shock
• Actual Study Start Date: January 1, 2020
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 48 hours of treatment [ Time Frame: 48 hours ]
   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.

Secondary Outcome Measures :

1. Change in organ dysfunction [ Time Frame: 10 days ]
   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.
2. Lactate clearance [ Time Frame: 10 days ]
   Improving lactate clearance by lowering serum lactate levels
3. Renal replacement therapy [ Time Frame: 10 days ]
   Time with need for renal replacement therapy
4. Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 24 hours of treatment [ Time Frame: 24 hours ]
   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.
5. End of septic shock [ Time Frame: 10 days ]
   Time until shock resolution
6. ICU length of stay [ Time Frame: 90 days ]
   ICU length of stay
7. Time on mechanical ventilation [ Time Frame: 10 days ]
   Time on mechanical ventilation
8. Cumulative catecholamine dose [ Time Frame: 10 days ]
   Cumulative catecholamine dose
9. Overall and ICU mortality [ Time Frame: 90 days ]
   Overall and ICU mortality
10. Serum levels of administered anti-infectives [ Time Frame: 3 days ]
    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)
11. Change of plasma Interleukin-6 (IL6) level [ Time Frame: 10 days ]
    Change of plasma Interleukin-6 (IL6) level
12. Change of plasma Interleukin-10 (IL10) level [ Time Frame: 10 days ]
    Change of plasma Interleukin-10 (IL10) level
13. Change of plasma Procalcitonin (PCT) level [ Time Frame: 10 days ]
    Change of plasma Procalcitonin (PCT) level
14. Change of HLA-DR level [ Time Frame: 10 days ]
    Change of HLA-DR (Human Leukocyte Antigen - DR isotype) level of monocytes
15. Change of TNF alpha level after ex-vivo stimulation [ Time Frame: 10 days ]
    Change of TNF-alfa level (Tumor Necrosis Factor alpha) level after LPS (Lipopolysaccharides) stimulation as sign of monocytic immunocompetence

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Dominik Jarczak, MD; +49 40 741035315; d.jarczak@uke.de

Contact: Axel Nierhaus, MD; +49 40 741035315; nierhaus@uke.de

Locations

Germany

University Medical Center Hamburg-Eppendorf; Recruiting

Hamburg, Germany

Contact: Dominik Jarczak, MD +49 40 741035315 d.jarczak@uke.de

Contact: Axel Nierhaus, MD +49 40 741035315 nierhaus@uke.de

Principal Investigator: Stefan Kluge, MD

Sub-Investigator: Dominik Jarczak, MD

Sub-Investigator: Axel Nierhaus, MD

Sub-Investigator: Christina König, MD

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

CytoSorbents, Inc

Investigators

• Principal Investigator: Stefan Kluge, MD; University Hospital Hamburg-Eppendorf, Department of Intensive Care Medicine

More Information

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.

• Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• ClinicalTrials.gov Identifier: NCT04013269
• Other Study ID Numbers: ACYSS; DRKS00015483 ( Registry Identifier: Deutsches Register Klinischer Studien )
• First Posted: July 9, 2019
• Last Update Posted: November 8, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:

Sepsis; Critically ill; Intensive care medicine; CytoSorb; Hemoadsorption; Pharmacokinetic

Additional relevant MeSH terms:

Shock, Septic; Shock; Pathologic Processes; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation