Could cytokines removal therapy by CytoSorb adsorber cause any improvement in the microcirculation?
ID
Source
Brief title
Condition
- Other condition
- Bacterial infectious disorders
- Nephropathies
Synonym
Health condition
Microcirculatie en weefseldoorbloeding
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Is cytokine removal with a CytoSorb adsorber during septic shock with AKI able
to alter the pathophysiologic changes of the microcirculation?
Secondary outcome
• To determine the systemic attenuation of cytokine concentrations in patients
with septic shock and AKI initiated on CVVHD in combination with the CytoSorb
membrane
• To investigate possible adsorption of Neutrophil Gelatinase-associated
Lipocalin by the CytoSorb membrane
• Determining the effect on ICU outcome, length of stay and SOFA score.
Background summary
Pathogenesis of septic shock and septic AKI are highly related to high-level of
cytokines release causing dysregulation of both pro-and anti-inflammatory
responses during sepsis. Supra-high concentrations of a variety of cytokines
upregulate the immunity and play an important role in the causality of the
sepsis syndrome itself.
Based on this, extra corporeal blood purification therapies (ECBPTs) are
intended to remove non-specifically a variety of low and middle molecular
substances including cytokines to diminish the high peaks. One of the
hemoadsorption techniques is The CytoSorb* technology (CytoSorbents
Corporation, Monmouth Junction, NJ, USA).
This technique is routinely used in many countries in cases where cytokine
levels are elevated especially in patients with septic shock. Animal studies
and many case reports have shown that CytoSorb significantly reduces cytokine
levels and improves global hemodynamics while improving the outcome.
Microcirculation is deteriorated in septic conditions due to several
mechanisms. To measure this we will use a new technologically advanced version
of hand held microscopes (CytoCam, Braedius Medical, Huizen, the Netherlands)
based on Incident Dark Field (IDF) by quantifying images to provide the needed
microcirculatory parameters directly at the bedside.
We will investigate the effect of cytokines removing therapy with the CytoSorb
adsorbing membrane on the improvement of the microcirculation in patients with
septic shock and AKI.
Study objective
Could cytokines removal therapy by CytoSorb adsorber cause any improvement in
the microcirculation?
Study design
Multi-center, comparison study as prove of concept.
Intervention
Data obtained in septic shock patients with AKI treated with CVVHD+ CytoSorb
(group 1) will be compared with microcirculatory measurements and biomarkers
obtained in septic shock patients with AKI without CytoSorb treatment (group
2).
Study burden and risks
The patients will be randomized into two groups. The first group will have a
CytoSorb filter added to the routine CRRT which has to be prepared by nurses
who are exclusively trained for this by CytoSorb company. The second group is
well known by the medical and nursing staff. They have large experience with
the use of CRRT in patients with septic shock and AKI. All the patients in the
two groups will be monitored continuously at the ICU. The CytoSorb filter will
be used in our Fresenius CRRT machines. In rare cases, hypersensitivity
reactions may occur during CytoSorb treatment. A history of allergies will be
carefully monitored at inclusion and during the study. Microcirculation
assessment is a non-invasive procedure, and there are negligible risks. Blood
and urine tests will be used for measuring cytokine, biomarkers, and drug
levels. The risks associated with participation can be considered negligible.
Bölschestrasse 116
Berlin 12587
NL
Bölschestrasse 116
Berlin 12587
NL
Listed location countries
Age
Inclusion criteria
Each patient, weight above 60 kg with septic shock needing vasopressors or
lower dosis norepinephrine supplemented with dobutamine, vasopressin
(argipressin) /terlipressin/epinephrine must meet all of the following criteria
to be enrolled in this study:
1. Has written informed consent from patient or legal representative.
2. Is aged 18 to 85 years, inclusive a weight above 60 kg.
3. Is admitted to the ICU
4. Has diagnosis of septic shock according to the criteria defined by Singer et
al in the Third International Consensus Definitions for Sepsis and Septic Shock
(Sepsis-3) published in JAMA, 2016.
• Organ dysfunction acute change in total SOFA score >=2 points consequent to
the infection or Quick SOFA (qSOFA,): alteration in mental status, systolic
blood pressure <=100 mm Hg, or respiratory rate >=22/min.
• Patients with septic shock can be identified with a clinical construct of
sepsis with persisting hypotension requiring vasopressors to maintain MAP >=65
mm Hg and having a serum lactate level >2 mmol/L despite adequate volume
resuscitation.
5. Has diagnosis of AKI, defined as the following:
AKI Stage 2 according to the following KDIGO guidelines criteria, based on
changes in Serum Creatinine (SCr), urine output or both:
a. Increase in SCr 2.0-2.9 times baseline and or a Urine Output (UO) < 0.5
ml-kg-h for >= 12 hours compared with a SCr value within the previous 48 hours.
b. The reference SCr value is a SCr value in the following order of preference:
1. Lowest value within 3 months of hospital admission if not available:
2. At hospital admission. If not available:
3. At ICU admission. If not available:
4. Lowest value between 3 and 12 months prior to hospital admission
6. Has a deteriorated sublingual microcirculation measured by Cytocam-IDF
imaging and quantified by determining the MFI as < 2,6.
Exclusion criteria
Patients meeting any of the following criteria will be excluded from the study:
1. Moribund
2. Woman of childbearing potential with a positive pregnancy test
3. Has a diagnosis of septic shock longer than 24 hours before inclusion
4. Has a normal sublingual microcirculation
5. Neutropenia; absolute neutrophil count less than 1000/um
6. Thrombocytopenia (less than 20.000/um)
7. Any body weight lower than 60 kg.
8. Treatment with intravenous aminoglycosids or antifungal therapy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL61004.078.17 |