Can Measurement of Neutrophil-derived ROS Production be a Novel Biomarker of Sepsis?

NCT05968287 | Completed

• 1 other identifier: GaziUtipNBDundar002
• Study Type: observational
• Target: 276
• Locations: 1 country
• Sites: 1

Brief Summary

Neutrophils are indispensable for host defense and have an important roles in modulating the immune system in both the innate and adaptive immune response. Neutrophils operate using a number of different mechanisms including chemotaxis, phagocytosis, release of reactive oxygen species (ROS) and granular proteins, and the production and liberation of cytokines for this purpose. A controlled neutrophil response is required to combat infection; an dysregulated state of this response can cause sepsis, tissue damage, and organ failure. Sepsis and septic shock are the leading causes of death especially in intensive care units (ICU), and their mortality can be reduced with prompt diagnosis and appropriate treatment modality. From this point of view, many biomarkers have been evaluated for the diagnosis, prognosis, and treatment response of infection and sepsis. An objective marker of cellular dysfunction of neutrophils would be a helpful tool for the clinician in detecting and monitoring changes related to infection status and to determine development of sepsis and positive effects of interventions.

Conditions

Infections; Sepsis; Septic Shock

Keywords

cellular dysfunction of neutrophils; reactive oxygen species (ROS); sepsis; septic shock; infections; biomarker

Outcome Measures

Primary Outcomes (2)

• the reactive oxygen species (ROS) production of neutrophils via the Leukocyte ImmunoTest™ (LIT)

  the difference of the Leukocyte ImmunoTest™ (LIT) as relative light unit (RLU) between patients with various infection conditions and control groups without infection. Abnormally high (hyperproduction) ROS generation demonstrated via The Leukocyte ImmunoTest™ (LIT) is associated with infection. LIT scores as relative light unit (RLU) can vary between 1-15000.

  Patients' LIT scores in relative light units (RLU) within 24 hours following the day of hospitalization during the study period

• the reactive oxygen species (ROS) production of neutrophils via the Leukocyte ImmunoTest™ (LIT)

  the difference of the Leukocyte ImmunoTest™ (LIT) as relative light unit (RLU) between patients between sepsis and without sepsis Abnormally high (hyperproduction) ROS generation demonstrated via The Leukocyte ImmunoTest™ (LIT) is associated with sepsis and septic shock. LIT scores as relative light unit (RLU) can vary between 1-15000.

  LIT score as as relative light unit (RLU) of the day of detecting of infection and sepsis up to 8 months

Secondary Outcomes (1)

• the reactive oxygen species (ROS) production of neutrophils via the Leukocyte ImmunoTest™ (LIT)

  the Leukocyte ImmunoTest™ (LIT) as relative light unit (RLU) of the patients with sepsis on every day or every other day up to death or discharge from the hospital through the study completion, an average of 8 months

Study Arms (2)

patient group

patients admitted to hospital with various infection conditions with or without sepsis

Diagnostic Test: The Leukocyte ImmunoTest™ (LIT™)

control group

patients admitted to hospital with various non-infectious diseases and outpatients who admitted to the outpatient clinics

Diagnostic Test: The Leukocyte ImmunoTest™ (LIT™)

Interventions

The Leukocyte ImmunoTest™ (LIT™) DIAGNOSTIC_TEST

The baseline LIT scores was performed for two parallel groups. The sequential LIT score was also performed for patients with various infection conditions with/without sepsis.

control group; patient group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patient population is consisted of patients who were admitted to the ICU or inward due various infectious etiologies. The control population is consisted of outpatients or inpatients admitted to ICU or inward for noninfectious etiologies.

You may qualify if:

• Diagnosis or suspicion of various infectious disease with or without sepsis and admitted to the ICU or inpatient service due to this clinical diagnosis for patient group
• Patients followed in the inpatient service due to various non-infectious diseases and outpatients who were examined in outpatient clinics for control group

You may not qualify if:

• patient or control group under the age of 18 years
• Patients died within the 24 hours after hospital admission
• Patients who did not sign informed consent
• Refusal of legal representative to participate in the study in unconscious patients
• Patients with an absolute neutrophil count \<500/mm3 on admission
• Control group describing any infective symptoms
• Control group with a chronic infectious disease under treatment

Sponsors & Collaborators

• Gazi University: lead
• Seroxo Ltd: collaborator

Study Sites (1)

Gazi University

Ankara, Yenimahalle, 06560, Turkey (Türkiye)

Location

Related Publications (11)

• Mortaz E, Alipoor SD, Adcock IM, Mumby S, Koenderman L. Update on Neutrophil Function in Severe Inflammation. Front Immunol. 2018 Oct 2;9:2171. doi: 10.3389/fimmu.2018.02171. eCollection 2018.

  PMID: 30356867 BACKGROUND

• Selders GS, Fetz AE, Radic MZ, Bowlin GL. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen Biomater. 2017 Feb;4(1):55-68. doi: 10.1093/rb/rbw041.

  PMID: 28149530 BACKGROUND

• Hellebrekers P, Vrisekoop N, Koenderman L. Neutrophil phenotypes in health and disease. Eur J Clin Invest. 2018 Nov;48 Suppl 2(Suppl Suppl 2):e12943. doi: 10.1111/eci.12943. Epub 2018 May 25.

  PMID: 29682724 BACKGROUND

• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.

  PMID: 34599691 BACKGROUND

• Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014 Aug;42(8):1749-55. doi: 10.1097/CCM.0000000000000330.

  PMID: 24717459 BACKGROUND

• Pierrakos C, Velissaris D, Bisdorff M, Marshall JC, Vincent JL. Biomarkers of sepsis: time for a reappraisal. Crit Care. 2020 Jun 5;24(1):287. doi: 10.1186/s13054-020-02993-5.

  PMID: 32503670 BACKGROUND

• Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, Allegranzi B, Reinhart K. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020 Aug;46(8):1552-1562. doi: 10.1007/s00134-020-06151-x. Epub 2020 Jun 22.

  PMID: 32572531 BACKGROUND

• Rhee C, Chiotos K, Cosgrove SE, Heil EL, Kadri SS, Kalil AC, Gilbert DN, Masur H, Septimus EJ, Sweeney DA, Strich JR, Winslow DL, Klompas M. Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure. Clin Infect Dis. 2021 Feb 16;72(4):541-552. doi: 10.1093/cid/ciaa059.

  PMID: 32374861 BACKGROUND

• Biomarkers Definitions Working Group.. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89-95. doi: 10.1067/mcp.2001.113989. No abstract available.

  PMID: 11240971 BACKGROUND

• Veenith T, Martin H, Le Breuilly M, Whitehouse T, Gao-Smith F, Duggal N, Lord JM, Mian R, Sarphie D, Moss P. High generation of reactive oxygen species from neutrophils in patients with severe COVID-19. Sci Rep. 2022 Jun 21;12(1):10484. doi: 10.1038/s41598-022-13825-7.

  PMID: 35729319 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

MeSH Terms

Conditions

Infections; Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Nazlıhan Boyacı Dündar, assist.prof.

  principle investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistan professor, Division of Intensive Care Medicine (principle invastigator)

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: August 1, 2023
• Study Start: June 28, 2022
• Primary Completion: January 27, 2023
• Study Completion: January 31, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)