Sepsis Clinical Trial
— EndoSorbOfficial title:
An Open-label Randomized Controlled Experimental Endotoxemia Study on the Effects of the Cytokine-adsorber CytoSorb on the Development of Immunoparalysis in Humans
Verified date | March 2021 |
Source | Radboud University Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
In this randomized, open-label study, the investigators will assess whether CytoSorb hemoperfusion will prevent or attenuate the development of immunoparalysis in healthy volunteers undergoing repeated experimental endotoxemia.
Status | Completed |
Enrollment | 24 |
Est. completion date | October 19, 2022 |
Est. primary completion date | October 19, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 18 Years to 35 Years |
Eligibility | Inclusion Criteria: - Provide written informed consent - Male - Age = 18 and = 35 years - Healthy (as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) and routine clinical laboratory parameters) Exclusion Criteria: - Use of any medication - Smoking - Known anaphylaxis or hypersensitivity to any (non-)investigational products or their excipients. - History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema) - History or signs of hematological disease - History or signs of thromboembolic disorders - History of (intracranial) aneurysmal or hemorrhagic diseases - History of heparin-induced thrombocytopenia (HIT) - Thrombocytopenia (<150*109/ml) or anemia (hemoglobin < 8.0 mmol/L) - History, signs or symptoms of cardiovascular disease, in particular: - Previous spontaneous vagal collapse - History of atrial or ventricular arrhythmia - Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrio-ventricular block or a complete left bundle branch block - Hypertension (defined as RR systolic > 160 or RR diastolic > 90 mmHg) - Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg) - Renal impairment (defined as plasma creatinine >120 µmol/l) - Liver enzyme abnormalities (above 2x the upper limit of normal) - Medical history of any disease associated with immune deficiency - Signs of infection (CRP > 20 mg/L, WBC > 12x109/L or < 4x109/L) - Clinically significant acute illness, including infections or trauma, within 1 month of the first endotoxin challenge - Previous (participation in a study with) endotoxin (LPS) administration - Any vaccination within 3 months within of the first endotoxin challenge - Participation in a drug trial or donation of blood within 3 months prior to first endotoxin challenge - Recent hospital admission or surgery with general anesthesia within 3 months prior to first endotoxin challenge - Use of recreational drugs within 1 month of the first endotoxin challenge - Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study. |
Country | Name | City | State |
---|---|---|---|
Netherlands | Radboud University Medical Center | Nijmegen | Gelderland |
Lead Sponsor | Collaborator |
---|---|
Radboud University Medical Center | CytoSorbents Europe GmbH |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Between group differences in plasma interleukin (IL)-6 levels during the second endotoxin challenge. | 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. | Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in plasma levels of other inflammatory cytokines during the second endotoxin challenge. | Interleukin (IL)-6, IL-8, IL-10, Monocyte Chemoattractant Protein (MCP)-1, C-X-C motif chemokine ligand (CXCL)-10, Macrophage Inflammatory Protein (MIP)-1a, MIP-1ß, and Granulocyte Colony-Stimulating Factor (G-CSF) | Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in mHLA-DR expression | Differences in Human Leukocyte Antigen (HLA)-DR expression on monocytes will be assessed using flowcytometry. | 1 hour before, 3 hours after and 6 hours after endotoxin administration | |
Secondary | Between group differences in norepinephrine sensitivity | To assess the effects of CytoSorb hemoperfusion on norepinephrine sensitivity, norepinephrine will be administered in increasing dosages (0.025; 0.05 and 0.1 ?) for 5 minutes per dose. Blood pressure will be recorded continuously with an arterial catheter. | One hour before and 4 hours after endotoxin administration during the first endotoxin challenge | |
Secondary | Cytokine clearance by the adsorber | Blood samples will be obtained from the afferent and efferent tubing of the CytoSorb adsorber to calculate clearance of cytokines by the adsorber | Every 30 minutes until cessation of hemoperfusion (six hours after endotoxin administration) | |
Secondary | Between group differences in endotoxemia-induced metabolic activity of platelets | Blood samples will be collected in citrated tubes to allow assessment of ATP production by platelets. | 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in endotoxemia-induced clinical symptoms | 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. | Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in body temperature | Body temperature will be assessed using tympanic temperature measurements | Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in blood pressure | Systolic, diastolic and mean arterial pressure will be measured continuously using a radial artery catheter. | From 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in heart rate | Heart rate will be recorded continuously using a 3-lead ECG. | From 1 hour prior until 8 hours after endotoxin administration | |
Secondary | Between group differences in markers of endothelial injury | Vascular cell adhesion protein (VCAM)-1 and Intercellular Adhesion Molecule (ICAM)-1 | Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration |
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