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Adjuvant Therapy With CytoSorb in Refractory Septic Shock

Not Applicable
Recruiting
Conditions
Septic Shock
Interventions
Device: CytoSorb-Therapy
Registration Number
NCT04013269
Lead Sponsor
Universitätsklinikum Hamburg-Eppendorf
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
32
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CytoSorb-TherapyCytoSorb-TherapyTherapy of septic shock using guideline directed standard of care, including continuous renal replacement therapy in combination with haemadsorption using CytoSorb-Adsorber
Primary Outcome Measures
NameTimeMethod
Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 48 hours of treatment48 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
NameTimeMethod
Renal replacement therapy10 days

Time with need for renal replacement therapy

End of septic shock10 days

Time until shock resolution

Overall and ICU mortality90 days

Overall and ICU mortality

Percentage of patients with a reduction of catecholamine dose of at least 25% within the first 24 hours of treatment24 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.

Change of plasma Interleukin-10 (IL10) level10 days

Change of plasma Interleukin-10 (IL10) level

Change of plasma Procalcitonin (PCT) level10 days

Change of plasma Procalcitonin (PCT) level

Change of HLA-DR level10 days

Change of HLA-DR (Human Leukocyte Antigen - DR isotype) level of monocytes

Lactate clearance10 days

Improving lactate clearance by lowering serum lactate levels

Serum levels of administered anti-infectives3 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)

Change in organ dysfunction10 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.

ICU length of stay90 days

ICU length of stay

Time on mechanical ventilation10 days

Time on mechanical ventilation

Cumulative catecholamine dose10 days

Cumulative catecholamine dose

Change of plasma Interleukin-6 (IL6) level10 days

Change of plasma Interleukin-6 (IL6) level

Change of TNF alpha level after ex-vivo stimulation10 days

Change of TNF-alfa level (Tumor Necrosis Factor alpha) level after LPS (Lipopolysaccharides) stimulation as sign of monocytic immunocompetence

Trial Locations

Locations (1)

University Medical Center Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

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