Assessing the Effects of CytoSorb Hemoperfusion on the Development on Immunoparalysis

NCT ID: NCT04643639

Last Updated: 2022-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-16
• Study Completion Date: 2022-10-19

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.

Detailed Description

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.

Conditions

Sepsis; Immune Deficiency; Hemoperfusion; Blood Purification

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active

Group Type: EXPERIMENTAL

CytoSorb hemoperfusion

Intervention Type: 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.

Control

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

CytoSorbents Europe GmbH

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Pickkers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 36945034 (View on PubMed)

Other Identifiers

The EndoSorb Study

Identifier Type: -

Identifier Source: org_study_id