Removal Of CytoKines With cytoSorbenTs After Inflammatory Response Reaction During Cardiac Surgery

Inflammatory Response Clinical Trial

— ROCKSTAR  

Official title:

Removal of Cytokines With Cytosorbents After Inflammatory Response Reaction During Cardiac Surgery and Association of Endothelial Progenitor Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06286280
• Other study ID #: AZ221/21
• Secondary ID: F/23/22
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2023
• Est. completion date: May 1, 2025

Study information

• Verified date: March 2024
• Source: University of Giessen
• Contact: Zulfugar T Taghiyev, MD, MBA
• Phone: +4964198556743
• Email: gk5019[@]uni-giessen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 >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).

Related Conditions & MeSH terms

• Inflammatory Response

Intervention

Device:
• cytokine adsorber (CytoSorb®)
binding of cytokines to the sorbent polystyrene of the adsorber during cardiac surgery with extracorporeal circulation

Locations

Country	Name	City	State
Germany	Universityhospital Giessen, Department of Cardiovascular Surgery	Giessen

Sponsors (2)

Lead Sponsor	Collaborator
University of Giessen	Deutsche Stiftung für Herzforschung

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	correlation of endothelial progenitor cells with cytokine levels with and without adsorber use	How does the number of EPCs during adsorber use correlate with cytokine levels, and how does the adsorber influence the time course of EPC release (measurement before and after adsorber use)?	24 hours before until day 7 post-surgery
Secondary	Overall mortality rate	Overall mortality rate until day 30	until day 30 post surgery
Secondary	Days on ventilator, vasopressor and renal replacement therapy	Total days on ventilator, vasopressor and renal replacement therapy within 30 days post-surgery will be assessed	until day 30 post-surgery
Secondary	incidence of stroke	incidence of stroke within 30 days post-surgery will be assessed	until day 30 post-surgery
Secondary	length of ICU and in-hospital stay	total length of ICU and in-hospital stay until day 30 post-surgery	until day 30 post-surgery
Secondary	Echocardiographic changes	Does a cytokine adsorber influence left ventricular function?	24 hours before until day 7 post-surgery
Secondary	Influence of Cytokine on endothelial progenitor cells	Does a cytokine adsorber influence EPC function? After isolation (CD34 sorting) and cultivation in stem cell medium, EPCs will be functionally characterized using angiogenesis assays (sprouting assay; tube formation), migration assays and measurement of DiI-Ac-LDL uptake.	24 hours before and immediately after surgery