Assessing the Effects of CytoSorb Hemoperfusion on the Development on Immunoparalysis (EndoSorb)
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|ClinicalTrials.gov Identifier: NCT04643639|
Recruitment Status : Recruiting
First Posted : November 25, 2020
Last Update Posted : March 12, 2021
|Condition or disease||Intervention/treatment||Phase|
|Sepsis Immune Deficiency Hemoperfusion Blood Purification||Device: CytoSorb hemoperfusion||Phase 3|
Sepsis is an inflammatory syndrome with high mortality rates and increasing incidence. Sepsis-induced immunoparalysis, increasingly recognized as the overriding immune disorder in sepsis patients, attributes significantly to late mortality in sepsis patients.
The investigators hypothesize that 'blood purification' techniques targeted at the removal of excess circulating cytokines, such as the CytoSorb hemoperfusion device, might prevent or attenuate the development of immunoparalysis.
The objective of this trial is to determine the effects of CytoSorb hemoperfusion on the development of immunoparalysis in a repeated experimental endotoxemia model in healthy male volunteers.
To this end, 24 healthy male volunteers subjects will be randomized in a 1:1 fashion into one of two treatment groups (active or control). Both study groups will undergo two endotoxin challenges, separated by seven days. To this end, endotoxin (LPS) will be administered as a bolus of 1 ng/kg, followed by continuous infusion of 0.5 ng/kg/hr for three hours. The active group will be treated with CytoSorb hemoperfusion during the first endotoxin challenge, whereas the control group will receive no additional treatment. During both endotoxin challenges, blood samples will be obtained serially to measure levels of circulating cytokines and other inflammatory mediators.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Randomized Controlled Experimental Endotoxemia Study on the Effects of the Cytokine-adsorber CytoSorb on the Development of Immunoparalysis in Humans|
|Actual Study Start Date :||September 16, 2020|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||August 31, 2021|
Device: CytoSorb hemoperfusion
Subjects will be treated with CytoSorb hemoperfusion (in stand-alone setup) for 6 hours at a flow rate of 250 ml/min during endotoxemia.
|No Intervention: Control|
- Between group differences in plasma interleukin (IL)-6 levels during the second endotoxin challenge. [ Time Frame: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration ]Blood samples will be obtained at predefined time points before, during and after endotoxin administration to assess plasma levels (in pg/mL) of circulating inflammatory mediatiors. To assess between group differences, the area under the curve (AUC) of the time concentration curve (expressed in arbitrary units) of each inflammatory mediator will be calculated.
- Between group differences in plasma levels of other inflammatory cytokines during the second endotoxin challenge. [ Time Frame: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration ]Interleukin (IL)-6, IL-8, IL-10, Monocyte Chemoattractant Protein (MCP)-1, C-X-C motif chemokine ligand (CXCL)-10, Macrophage Inflammatory Protein (MIP)-1α, MIP-1β, and Granulocyte Colony-Stimulating Factor (G-CSF)
- Between group differences in mHLA-DR expression [ Time Frame: 1 hour before, 3 hours after and 6 hours after endotoxin administration ]Differences in Human Leukocyte Antigen (HLA)-DR expression on monocytes will be assessed using flowcytometry.
- Between group differences in norepinephrine sensitivity [ Time Frame: One hour before and 4 hours after endotoxin administration during the first endotoxin challenge ]To assess the effects of CytoSorb hemoperfusion on norepinephrine sensitivity, norepinephrine will be administered in increasing dosages (0.025; 0.05 and 0.1 γ) for 5 minutes per dose. Blood pressure will be recorded continuously with an arterial catheter.
- Cytokine clearance by the adsorber [ Time Frame: Every 30 minutes until cessation of hemoperfusion (six hours after endotoxin administration) ]Blood samples will be obtained from the afferent and efferent tubing of the CytoSorb adsorber to calculate clearance of cytokines by the adsorber
- Between group differences in endotoxemia-induced metabolic activity of platelets [ Time Frame: 1 hour prior until 8 hours after endotoxin administration ]Blood samples will be collected in citrated tubes to allow assessment of ATP production by platelets.
- Between group differences in endotoxemia-induced clinical symptoms [ Time Frame: Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration ]Clinical symptoms will be scored on a Likert scale (ranging from 0 to 5) in a composite endpoint consisting of headache, nausea, shivering, muscle soreness and lower back pain. Higher numbers indicate more severe symptoms.
- Between group differences in body temperature [ Time Frame: Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration ]Body temperature will be assessed using tympanic temperature measurements
- Between group differences in blood pressure [ Time Frame: From 1 hour prior until 8 hours after endotoxin administration ]Systolic, diastolic and mean arterial pressure will be measured continuously using a radial artery catheter.
- Between group differences in heart rate [ Time Frame: From 1 hour prior until 8 hours after endotoxin administration ]Heart rate will be recorded continuously using a 3-lead ECG.
- Between group differences in markers of endothelial injury [ Time Frame: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration ]Vascular cell adhesion protein (VCAM)-1 and Intercellular Adhesion Molecule (ICAM)-1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04643639
|Contact: Aron Jansen, MDemail@example.com|
|Contact: Matthijs Kox, PhDfirstname.lastname@example.org|
|Radboud University Medical Center||Recruiting|
|Nijmegen, Gelderland, Netherlands, 6500HB|
|Contact: Aron Jansen, MD +31243616735 email@example.com|
|Sub-Investigator: Aron Jansen, MD|
|Principal Investigator:||Peter Pickkers, MD, PhD||Radboud University Medical Center|