SepsisPhase 3EndoSorbNCT04643639
Assessing the Effects of CytoSorb Hemoperfusion on the Development on Immunoparalysis
A Phase 3 study testing CytoSorb hemoperfusion in people with Sepsis and Immune Deficiency, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Immune Deficiency, Hemoperfusion
- What is being tested?
- CytoSorb hemoperfusion
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 16 Sep 2020to 19 Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 26Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Medical Center
Nijmegen, Gelderland, 6500HB
About this study
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
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.
Read the 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
- Being tested
- CytoSorb hemoperfusion
- Medical subject headings
- Sepsis, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytoSorb hemoperfusionDevice
Subjects will be treated with CytoSorb hemoperfusion (in stand-alone setup) for 6 hours at a flow rate of 250 ml/min during endotoxemia.
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | Not described Receives: Device: CytoSorb hemoperfusion |
| Control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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)
Measured: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration
Between group differences in mHLA-DR expression
Differences in Human Leukocyte Antigen (HLA)-DR expression on monocytes will be assessed using flowcytometry.
Measured: 1 hour before, 3 hours after and 6 hours after endotoxin administration
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 γ) for 5 minutes per dose. Blood pressure will be recorded continuously with an arterial catheter.
Measured: One hour before and 4 hours after endotoxin administration during the first endotoxin challenge
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
Measured: Every 30 minutes until cessation of hemoperfusion (six hours after endotoxin administration)
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.
Measured: 1 hour prior until 8 hours after endotoxin administration
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.
Measured: Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration
Between group differences in body temperature
Body temperature will be assessed using tympanic temperature measurements
Measured: Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration
Between group differences in blood pressure
Systolic, diastolic and mean arterial pressure will be measured continuously using a radial artery catheter.
Measured: From 1 hour prior until 8 hours after endotoxin administration
Between group differences in heart rate
Heart rate will be recorded continuously using a 3-lead ECG.
Measured: From 1 hour prior until 8 hours after endotoxin administration
Between group differences in markers of endothelial injury
Vascular cell adhesion protein (VCAM)-1 and Intercellular Adhesion Molecule (ICAM)-1
Measured: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start16 Sep 2020
- Primary completion19 Oct 2022
- Study completion19 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- CytoSorbents Europe GmbH
- Responsible party
- Sponsor
- Investigators
- Peter Pickkers, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04643639
- Sponsor's protocol ID
- The EndoSorb Study
- Acronym
- EndoSorb
- Status last verified
- Mar 2021
- First submitted
- 15 Sep 2020
- Last updated
- 22 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 36945034
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04643639
- Acronym / sponsor ID
- EndoSorb / The EndoSorb Study
- Conditions
- Sepsis, Immune Deficiency, Hemoperfusion, Blood Purification
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- CytoSorbents Europe GmbH
- Study start
- 16 Sep 2020 (actual)
- Primary completion
- 19 Oct 2022 (actual)
- Study completion
- 19 Oct 2022 (actual)
- First posted
- 25 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Device: CytoSorb hemoperfusion |
| Control | No intervention | – |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytoSorb hemoperfusionSubjects will be treated with CytoSorb hemoperfusion (in stand-alone setup) for 6 hours at a flow rate of 250 ml/min during endotoxemia. | Device | Active |
Primary outcome
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.
10 secondary outcomes
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
Between group differences in mHLA-DR expression
Time frame: 1 hour before, 3 hours after and 6 hours after endotoxin administration
Between group differences in norepinephrine sensitivity
Time frame: One hour before and 4 hours after endotoxin administration during the first endotoxin challenge
Cytokine clearance by the adsorber
Time frame: Every 30 minutes until cessation of hemoperfusion (six hours after endotoxin administration)
Between group differences in endotoxemia-induced metabolic activity of platelets
Time frame: 1 hour prior until 8 hours after endotoxin administration
Between group differences in endotoxemia-induced clinical symptoms
Time frame: Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration
Between group differences in body temperature
Time frame: Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration
Between group differences in blood pressure
Time frame: From 1 hour prior until 8 hours after endotoxin administration
Between group differences in heart rate
Time frame: From 1 hour prior until 8 hours after endotoxin administration
Between group differences in markers of endothelial injury
Time frame: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2022.
- Derived from this study: PubMed 36945034Jansen 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.
- Individual participant dataSharing planned: Undecided
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Pickkers, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CytoSorb hemoperfusion in people with Sepsis and Immune Deficiency, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04643639, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2022.