Adjuvant Therapy With CytoSorb in Refractory Septic Shock

Septic Shock Clinical Trial

— ACYSS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04013269
• Other study ID #: ACYSS
• Secondary ID: DRKS00015483
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2020
• Est. completion date: December 2023

Study information

• Verified date: November 2022
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: Dominik Jarczak, MD
• Phone: +49 40 741035315
• Email: d.jarczak[@]uke.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Device:
• CytoSorb-Therapy
Additional use of Cytosorb-Adsorber in patients with septic shock and need for continuous renal replacement therapy

Locations

Country	Name	City	State
Germany	University Medical Center Hamburg-Eppendorf	Hamburg

Sponsors (2)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	CytoSorbents, Inc

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View Citation

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. — View Citation

Garau I, März A, Sehner S, Reuter DA, Reichenspurner H, Zöllner C, Kubitz JC. Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor a 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. — View Citation

Kogelmann K, Jarczak D, Scheller M, Drüner 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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Lactate clearance	Improving lactate clearance by lowering serum lactate levels	10 days
Secondary	Renal replacement therapy	Time with need for renal replacement therapy	10 days
Secondary	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
Secondary	End of septic shock	Time until shock resolution	10 days
Secondary	ICU length of stay	ICU length of stay	90 days
Secondary	Time on mechanical ventilation	Time on mechanical ventilation	10 days
Secondary	Cumulative catecholamine dose	Cumulative catecholamine dose	10 days
Secondary	Overall and ICU mortality	Overall and ICU mortality	90 days
Secondary	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
Secondary	Change of plasma Interleukin-6 (IL6) level	Change of plasma Interleukin-6 (IL6) level	10 days
Secondary	Change of plasma Interleukin-10 (IL10) level	Change of plasma Interleukin-10 (IL10) level	10 days
Secondary	Change of plasma Procalcitonin (PCT) level	Change of plasma Procalcitonin (PCT) level	10 days
Secondary	Change of HLA-DR level	Change of HLA-DR (Human Leukocyte Antigen - DR isotype) level of monocytes	10 days
Secondary	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