Clinical trial NCT06286280: Removal Of CytoKines With cytoSorbenTs After Inflammatory Response Reaction During Cardiac Surgery
Official title: Removal of Cytokines With Cytosorbents After Inflammatory Response Reaction During Cardiac Surgery and Association of Endothelial Progenitor Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammatory Response
Keywords: CD34+ endothelial progenitor cells
systemic inflammation
extracorporeal circulation
Lead sponsor: University of Giessen
Sponsor class: OTHER
Collaborators: name: Deutsche Stiftung für Herzforschung
First posted: 2024-02-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-center, two-arm randomized-controlled prospective study
Primary purpose: BASIC_SCIENCE

Brief summary: Detailed knowledge about the association between systemic inflammation and endothelial progenitor cell (EPCs) activation during extracorporeal circulation (ECC) is lacking.

This pilot study aims to clarify the relationship between CD34-positive EPCs and cytokine release during ECC using the cytokine adsorber to make a predictive statement regarding the clinical expression of inflammation.

Detailed description: Mechanical cardiovascular support procedures are used as part of cardiac surgery. Here, heart-lung machines (HLM) and miniaturized systems such as ECMO (extracorporeal membrane oxygenation) are used to replace cardiac and/or pulmonary function. Contact with non-physiologic artificial surfaces can induce a generalized 'sterile' inflammatory syndrome called SIRS (Systemic Inflammatory Response Syndrome). During SIRS, proinflammatory cytokine release occurs due to complement activation. These massively released, diverse cytokines significantly influence the activation and release of endothelial progenitor cells (EPCs) from the bone marrow during extracorporeal circulation (ECC) and their long-term functionality.

The life-threatening complications of the so-called cytokine storm can potentially be avoided with the help of a cytokine adsorber (CytoSorb®), and the stabilization process after the hyperinflammatory phase can be promoted. However, it is unclear the quantitative and qualitative modification of the cytokine expression pattern by the use of the cytokine adsorber and its influence on the release of EPCs as well as on the clinical course of the patients. Although a therapy extension with cytokine adsorber has a positive impact on the reduction of cytokine levels in the blood, cytokine removal has not been investigated in direct correlation to EPCs.

These interactions are to be investigated within the scope of the proposed project.

This project is a pilot study with a translational science background to clarify the relationship between CD34-positive endothelial progenitor cells and cytokine release in the setting of ECCs using cytokine adsorber. Previous studies have shown a positive association between increased cytokine levels and the number of circulating endothelial progenitor cells. To date, it has not been investigated how this correlation or association changes with the use of cytokine adsorbers. Therefore, due to the specificity of targeted cytokine removal, the findings obtained here may provide essential insights in basic clinical research that could be applied to clinical issues and decision-making processes in the future. Due to the increasingly important role of extracorporeal circulatory support systems, detailed knowledge of the relationship between systemic inflammation and endothelial progenitor cell activation during their use will be increasingly important in the future.

The current project aims to investigate whether an association between the inflammatory response during and after cardiac surgery and the number of stem cells (EPCs) continues to exist when the cytokine adsorber (CytoSorb®) is applied and whether and how the adsorber can influence the functionality, migratory capacity, and differentiation of stem cells. We assume that under these conditions, a direct correlation of EPCs with inflammation does not exist, so a modulation of the SIRS (Systemic Inflammatory Response Syndrome) clinically observed by us could be absent. In addition, we will investigate whether a correlation between the number of circulating endothelial progenitor cells (CD 34+ cells) and the concentration of cytokines can be observed to make a predictive statement regarding the clinical expression of inflammation.

The long-term goal is to identify patients at high risk for clinical manifestations of inflammation after using the EPC and, based on the knowledge gained, make a predictive statement based on the concentration pattern of the EPC.

This prospective study should provide information on whether and at which point perioperative hyperinflammation can be reliably predicted and whether establishing a specific cytokine adsorber could positively influence the number of EPCs and, thus, short- and medium-term survival.

Eligibility criteria: Inclusion Criteria:

* planned cardiac surgical procedure with the use of the cardiopulmonary machine as well as with ECMO use (elective or urgent)
* age at the time of surgery of \&gt;18 years.
* informed consent

Exclusion Criteria:

* An emergency indication;
* endocarditis, a non-sterile inflammation,
* autoimmune diseases, chronic inflammatory diseases (ankylosing spondylitis, psoriasis, rheumatoid arthritis, chronic inflammatory intestinal diseases), an acquired immune deficit (HIV);
* severe liver dysfunction, hepatitis B/0;
* patients on dialysis;
* Patients with a hematopoietic disorder/tumour disease;
* participation in other interventional trials or studies;
* timely and probable follow-up cannot be guaranteed (e.g. due to long distances between home and study site); a pregnancy that cannot be excluded with certainty (no menopause, no sterilization).

Primary outcomes:
measure: correlation of endothelial progenitor cells with cytokine levels with and without adsorber use
timeFrame: 24 hours before until day 7 post-surgery
Secondary outcomes:
measure: Overall mortality rate
timeFrame: until day 30 post surgery
measure: Days on ventilator, vasopressor and renal replacement therapy
timeFrame: until day 30 post-surgery
measure: incidence of stroke
timeFrame: until day 30 post-surgery
measure: length of ICU and in-hospital stay
timeFrame: until day 30 post-surgery
measure: Echocardiographic changes
timeFrame: 24 hours before until day 7 post-surgery
measure: Influence of Cytokine on endothelial progenitor cells
timeFrame: 24 hours before and immediately after surgery
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: Universityhospital Giessen, Department of Cardiovascular Surgery
Study officials:
References: