Clinical trial NCT04013269: Adjuvant Therapy With CytoSorb in Refractory Septic Shock
Official title: Effect of the CytoSorb Adsorber on Hemodynamic, Immunological and Pharmacokinetic Parameters in Refractory Septic Shock
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Septic Shock
Keywords: Sepsis
Critically ill
Intensive care medicine
CytoSorb
Hemoadsorption
Pharmacokinetic
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: CytoSorbents, Inc
First posted: 2019-07-09
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 48 hours of treatment
timeFrame: 48 hours
Secondary outcomes:
measure: Change in organ dysfunction
timeFrame: 10 days
measure: Lactate clearance
timeFrame: 10 days
measure: Renal replacement therapy
timeFrame: 10 days
measure: Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 24 hours of treatment
timeFrame: 24 hours
measure: End of septic shock
timeFrame: 10 days
measure: ICU length of stay
timeFrame: 90 days
measure: Time on mechanical ventilation
timeFrame: 10 days
measure: Cumulative catecholamine dose
timeFrame: 10 days
measure: Overall and ICU mortality
timeFrame: 90 days
measure: Serum levels of administered anti-infectives
timeFrame: 3 days
measure: Change of plasma Interleukin-6 (IL6) level
timeFrame: 10 days
measure: Change of plasma Interleukin-10 (IL10) level
timeFrame: 10 days
measure: Change of plasma Procalcitonin (PCT) level
timeFrame: 10 days
measure: Change of HLA-DR level
timeFrame: 10 days
measure: Change of TNF alpha level after ex-vivo stimulation
timeFrame: 10 days
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: University Hospital Hamburg-Eppendorf, Department of Intensive Care Medicine
name: Stefan Kluge, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: 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.
citation: 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.