AOrtic Surgery: Systemic Inflammatory Response Versus Sepsis

NCT ID: NCT06028789

Last Updated: 2024-05-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2024-06-30

Brief Summary

The goal of the prospective observational study is to evaluate the immunological background of inflammatory response often seen after open thoracic aortic surgery. Patients scheduled for this type of procedure will undergo a series of blood testing (preoperatively, and several times postoperatively). The blood samples will be used for a wide scale of immunological tests to better evaluate potential differential markers against infection. A control group will include patients with active infective endocarditis (preoperatively).

The main question is if there is a biomarker able to determine a difference between sterile systemic inflammation and infection after thoracic aortic surgery. The second question is if there is a difference in dynamics of evaluated biomarkers between sterile postoperative inflammation and active endocarditis.

Detailed Description

It has been observed in daily clinical practice that patients after thoracic aortic replacement (of any extent, of any reason) often develop a set of specific symptoms. Those include fever, weakness and prolonged rise of standard laboratory parameters of inflammation (CRP and leucocyte level) in absence of infection. Those symptoms may, but do not have to, coincide with typical signs of postcardiotomy syndrome, rather characteristic by pericardial / pleural effusion and indifferent chest pain. They rather resemble a so called "postimplantation" syndrome, described after endovascular aortic repair. As a reaction to foreign vascular graft material, pro-inflammatory cytokines are being released, thus leading to flu-like symptoms in absence of true infection. Those occur in the short-term postoperatively, usually in the first 2 weeks after the surgery.

Patients after thoracic aortic surgery represent a high-risk patient cohort vulnerable to infections of any kind, mostly respiratory, urinary, wound infections, and, last but not least, early valve endocarditis / endoaortitis being the most feared of them. While clinicians (and patients) are often afraid of the abovementioned complications, the patients are forced to undergo complex diagnostic process including repeated echocardiography, collection of microbiology cultures and blood samples, chest computer tomography imaging with extensive radiation burden. The prolonged broad-spectrum empiric antibiotic treatment is often in place together with prolonged hospital stay and limited patient satisfaction. The question of starting the immunosuppressive treatment is often weighed against the potential aggravation of infection with eventual fatal consequences.

In absence of a specific biomarker to distinguish between the sterile systemic inflammation and infection, the clinicians must rely on complex evaluation of patient symptoms, clinical examination, imaging modalities, standard laboratory measures of inflammation and microbiology cultures (with some delay). However, in the era of molecular biology and extensive progress in immunology research, there has been a long row of potential biomarkers able to specify the etiology of inflammatory process significantly sooner.

The potential biomarkers of inflammation suitable for this issue are mentioned in detail further. Conventional biomarkers include CRP, leukocyte count, differential blood count, recently also procalcitonin (PCT), tumor necrosis factor-α (TNF- α) and interleukin-6 (IL-6). Hematology tests have reported novel early markers of sepsis, e.g. mean neutrophil volume or neutrophil-to-lymphocyte ratio. Novel serology markers (mostly assessed by ELISA) include soluble triggering receptor expressed on myeloid cell-1 (sTREM-1), presepsin, serum amyloid-A, pentraxin 3, hemoxygenase-1 (HO-1), soluble CD64 (sCD64), soluble CD163 (sCD163), high mobility group box-1 (HMGB-1), lipopolysaccharide-binding protein (LBP) and others. Newly, the molecules expressed on the surface of circulating blood cells may be examined using flow cytometry: CD64 on polymorphonuclears (PMN CD64 index) or monocytes, CD163, CD167, HLA-DR etc. Cell function assays which test ability of blood cells to respond to microbial stimuli (represented by LPS, flagellin, etc.) may reveal changes in soluble biomarkers, such as IL-18 or IFN-γ that reflect nature of inflammation in patients.

Recently, several scoring systems have emerged combining panels of various biomarkers. There is a promising evidence for a composite of serum and cell-expressed parameters, called "Bioscore", including procalcitonin, sTREM-1 and PMN CD64 index. A composite of 5 hematological parameters has proven to be a reliable marker of early sepsis, being called intensive care infection score (ICIS). Another scoring systems have been developed by group of Kofoed et al. Nevertheless, most of these scoring systems have been tested in the settings of unstable patients in the intensive care unit. The issue of inflammatory response described above is mostly a matter of stable patients in the standard ward who develop signs of undetermined inflammation. Eventual diagnostic modalities in these settings have been only scarcely evaluated before. The topic of inflammatory response after aortic surgery (IRAS) has not been studied in the literature yet.

Conditions

Systemic Inflammatory Response Syndrome; Infections; Thoracic Aortic Aneurysm; Aortic Diseases; Immunological Abnormality

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Study group

Patients undergoing elective thoracic aortic surgery.

Blood sample test

Intervention Type: DIAGNOSTIC_TEST

The following groups of biomarkers will be examined:

• standard panel of inflammation markers: CRP, PCT, IL-6, Leukocyte count, differential blood count
• microbiology cultures according to the clinical status
• serum biomarkers: sCD64, sTREM-1, calprotectin, pentraxin 3
• flow cytometry: HLA-DR, CD14, CD16, CD40, CD45, CD64, CD163 expression on granulocytes and monocytes
• cell function assay: IL-18 and IFN-γ
• hematology: ICIS, Neutrophil-to-lymphocyte ratio - examined together with conventional hematological parameters.

The schedule of blood sample taking will be as follows:

A. the study group: preoperatively (T-1), 1st postoperative day (T1), 3rd postoperative day (T2), 7th postoperative day (T3), 10th postoperative day (T4)

B. the control group: at admission or the next day (T1), 3rd day of hospital stay (T2), 7th day of hospital stay (T3), 10th day of hospital stay (T4)

Thoracic Aortic Surgery

Intervention Type: PROCEDURE

Scheduled surgical intervention, i.e. replacement of pre-specified part of thoracic aorta by a vascular prosthesis.

Control group

Patients admitted to our institution with active infectious endocarditis.

Blood sample test

Intervention Type: DIAGNOSTIC_TEST

The following groups of biomarkers will be examined:

• standard panel of inflammation markers: CRP, PCT, IL-6, Leukocyte count, differential blood count
• microbiology cultures according to the clinical status
• serum biomarkers: sCD64, sTREM-1, calprotectin, pentraxin 3
• flow cytometry: HLA-DR, CD14, CD16, CD40, CD45, CD64, CD163 expression on granulocytes and monocytes
• cell function assay: IL-18 and IFN-γ
• hematology: ICIS, Neutrophil-to-lymphocyte ratio - examined together with conventional hematological parameters.

The schedule of blood sample taking will be as follows:

A. the study group: preoperatively (T-1), 1st postoperative day (T1), 3rd postoperative day (T2), 7th postoperative day (T3), 10th postoperative day (T4)

B. the control group: at admission or the next day (T1), 3rd day of hospital stay (T2), 7th day of hospital stay (T3), 10th day of hospital stay (T4)

Interventions

Blood sample test

The following groups of biomarkers will be examined:

• standard panel of inflammation markers: CRP, PCT, IL-6, Leukocyte count, differential blood count
• microbiology cultures according to the clinical status
• serum biomarkers: sCD64, sTREM-1, calprotectin, pentraxin 3
• flow cytometry: HLA-DR, CD14, CD16, CD40, CD45, CD64, CD163 expression on granulocytes and monocytes
• cell function assay: IL-18 and IFN-γ
• hematology: ICIS, Neutrophil-to-lymphocyte ratio - examined together with conventional hematological parameters.

The schedule of blood sample taking will be as follows:

A. the study group: preoperatively (T-1), 1st postoperative day (T1), 3rd postoperative day (T2), 7th postoperative day (T3), 10th postoperative day (T4)

B. the control group: at admission or the next day (T1), 3rd day of hospital stay (T2), 7th day of hospital stay (T3), 10th day of hospital stay (T4)

Intervention Type: DIAGNOSTIC_TEST

Thoracic Aortic Surgery

Scheduled surgical intervention, i.e. replacement of pre-specified part of thoracic aorta by a vascular prosthesis.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• patient scheduled for elective replacement of thoracic aorta of any extent by artificial vascular graft, including Bentall procedure, Yacoub procedure, supracoronary aortic replacement, also Ross procedure with supracoronary aortic replacement, hemiarch and total aortic arch replacement
• signature of informed patient consent

• patient with active infectious endocarditis
• signature of informed patient consent

Exclusion Criteria

• active endocarditis or other infection
• unstable preoperative condition

• more than 5 days since diagnosis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Association for Thoracic Surgery

UNKNOWN

Sponsor Role: collaborator

University Hospital Hradec Kralove

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Vojacek, Prof. MD

Role: STUDY_CHAIR

University Hospital Hradec Kralove

Locations

University Hospital Hradec Králové

Hradec Králové, Královehradecký Kraj, Czechia

Site Status: RECRUITING

Countries

Czechia

Central Contacts

Jan Gofus, MD, PhD

Role: CONTACT

jan.gofus@gmail.com

+420 722 301 527

Andrej Myjavec, MD

Role: CONTACT

andrej.myjavec@fnhk.cz

Facility Contacts

Ján Gofus, MD, PhD

Role: primary

jan.gofus@fnhk.cz

+420495832422

References

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Reference Type: BACKGROUND

PMID: 31363326 (View on PubMed)

Daye D, Walker TG. Complications of endovascular aneurysm repair of the thoracic and abdominal aorta: evaluation and management. Cardiovasc Diagn Ther. 2018 Apr;8(Suppl 1):S138-S156. doi: 10.21037/cdt.2017.09.17.

Reference Type: BACKGROUND

PMID: 29850426 (View on PubMed)

Raveendran AV, Kumar A, Gangadharan S. Biomarkers and newer laboratory investigations in the diagnosis of sepsis. J R Coll Physicians Edinb. 2019 Sep;49(3):207-216. doi: 10.4997/JRCPE.2019.308.

Reference Type: BACKGROUND

PMID: 31497788 (View on PubMed)

Gibot S, Bene MC, Noel R, Massin F, Guy J, Cravoisy A, Barraud D, De Carvalho Bittencourt M, Quenot JP, Bollaert PE, Faure G, Charles PE. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med. 2012 Jul 1;186(1):65-71. doi: 10.1164/rccm.201201-0037OC. Epub 2012 Apr 26.

Reference Type: BACKGROUND

PMID: 22538802 (View on PubMed)

Nierhaus A, Linssen J, Wichmann D, Braune S, Kluge S. Use of a weighted, automated analysis of the differential blood count to differentiate sepsis from non-infectious systemic inflammation: the intensive care infection score (ICIS). Inflamm Allergy Drug Targets. 2012 Apr;11(2):109-15. doi: 10.2174/187152812800392841.

Reference Type: BACKGROUND

PMID: 22280231 (View on PubMed)

Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, Larsen K. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 2007;11(2):R38. doi: 10.1186/cc5723.

Reference Type: BACKGROUND

PMID: 17362525 (View on PubMed)

Djebara S, Biston P, Fosse E, Daper A, Joris M, Boudjeltia KZ, Lelubre C, Cauchie P, Piagnerelli M. Time Course of CD64, a Leukocyte Activation Marker, During Cardiopulmonary Bypass Surgery. Shock. 2017 Feb;47(2):158-164. doi: 10.1097/SHK.0000000000000751.

Reference Type: BACKGROUND

PMID: 27648690 (View on PubMed)

Kolackova M, Kudlova M, Kunes P, Lonsky V, Mandak J, Andrys C, Jankovicova K, Krejsek J. Early expression of FcgammaRI (CD64) on monocytes of cardiac surgical patients and higher density of monocyte anti-inflammatory scavenger CD163 receptor in "on-pump" patients. Mediators Inflamm. 2008;2008:235461. doi: 10.1155/2008/235461.

Reference Type: BACKGROUND

PMID: 18320015 (View on PubMed)

Other Identifiers

202202 P02

Identifier Type: -

Identifier Source: org_study_id