Assessing the Effects of CytoSorb Hemoperfusion on the Development on Immunoparalysis

NCT04643639 | Completed Phase 3 DMC FDA Device

• 1 other identifier: The EndoSorb Study
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sepsis; Immune Deficiency; Hemoperfusion; Blood Purification

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Between group differences in plasma levels of other inflammatory cytokines during the second endotoxin challenge.

  Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration

• Between group differences in mHLA-DR expression

  1 hour before, 3 hours after and 6 hours after endotoxin administration

• Between group differences in norepinephrine sensitivity

  One hour before and 4 hours after endotoxin administration during the first endotoxin challenge

• Cytokine clearance by the adsorber

  Every 30 minutes until cessation of hemoperfusion (six hours after endotoxin administration)

• Between group differences in endotoxemia-induced metabolic activity of platelets

  1 hour prior until 8 hours after endotoxin administration

Study Arms (2)

Active

EXPERIMENTAL

Device: CytoSorb hemoperfusion

Control

NO INTERVENTION

Interventions

CytoSorb hemoperfusion DEVICE

Subjects will be treated with CytoSorb hemoperfusion (in stand-alone setup) for 6 hours at a flow rate of 250 ml/min during endotoxemia.

Active

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead
• CytoSorbents Europe GmbH: collaborator

Study Sites (1)

Radboud University Medical Center

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Related Publications (1)

• Jansen A, Waalders NJB, van Lier DPT, Kox M, Pickkers P. CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo. Crit Care. 2023 Mar 21;27(1):117. doi: 10.1186/s13054-023-04391-z.

  PMID: 36945034 DERIVED

MeSH Terms

Conditions

Sepsis; Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: November 25, 2020
• Study Start: September 16, 2020
• Primary Completion: October 19, 2022
• Study Completion: October 19, 2022
• Last Updated: December 22, 2022

Record last verified: 2021-03

Locations

NL (1)