The Role of Post-traumatic Inhibition of the Innate and Adaptive Immune System in the Development of Infectious Complications in Severely Injured Patients (POSEIDON)

Patients admitted to the Intensive Care Unit after severe injury are prone to suffer from infectious complications and even sepsis. Despite tremendous efforts the etiology of this increased susceptibility to infectious pathogens is incompletely understood. Clinical signs and symptoms as well as current diagnostic clinical tests (WBC, CRP, cytokines, interleukines) lack sensitivity or specificity for adequate prediction of the development of infectious complications or sepsis.

Neutrophil granulocytes, cells of the innate immune system, play an important role in the defence against invading bacterial pathogens and are crucial in preventing fulminant infections. For successful eradication of a bacterium neutrophils need to exert specific functions: chemotaxis, migration, phagocytosis, degranulation and production of radical oxygen species. Much research has focused on the effect of trauma on neutrophil's individual capacities to kill bacteria with conflicting interpretations as a result. For adequate determination of the neutrophil's capacity to eradicate bacteria from tissue of trauma patients we developed novel in-vitro assays in which neutrophils are tested for all of these functions combined. This assay allows us to identify dysfunctional neutrophils adequately.

The main focus of this study is the determination of the functionality of aberrant neutrophils circulating in the peripheral blood of severly injured following trauma.

Study Overview

• Status: Terminated
• Conditions: Sepsis; Multiple Trauma; Innate Immune Response; Multiple Organ Dysfunction Syndrome; Disorder of Neutrophils

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3508 GA
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Trauma patients likely to be admitted to the intensive care unit of the UMCU

Description

Inclusion Criteria:

• Admitted to the ICU
• Expected stay of at least 2 days
• Age: 18 - 80 years
• Informed consent (when proxy consent is obtained and the patient leaves the ICU in good mental health, personal informed consent is additionally necessary)

Exclusion Criteria:

• Immunosuppressive medication
• HIV and related diseases

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bactericidal capacity of neutrophils and sepsis	The correlation between reduced bactericidal capacity of neutrophils acquired from severely injured patients and the late occurrence of sepsis	15 days following admission on ICU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bactericidal capacity of neutrophils and infectious complications	The correlation between reduced bacterial killing by neutrophils acquired from trauma patients and the occurrence of infectious complications (e.g pneumonia, meningitis, pericarditis, urinary tract infections, abdominal abscesses)	15 days following admission to the ICU
Bactericidal capacity of neutrophils and pro-inflammatory complications	The correlation between bactericidal function of neutrophils and the occurrence of pro-inflammatory complications (SIRS).	15 days following admission to the ICU
Priming capacity of neutrophils and infectious complications	The relationship between the responsiveness of neutrophils to a priming stimulus (fMLP) and the occurrence of infectious complications	15 days following admission on the ICU
Complement system and infectious complications	The correlation between functionality of the complement system and the occurence of infectious complications.	15 days following admission to the ICU
T-cell proliferation and infectious complications	The difference in suppression of T-cell proliferation in patients suffering infectious complications versus non-infectious patients.	15 days following admission on ICU

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Pieter Leliefeld, Md, UMC Utrecht; Study Chair: Luke PH Leenen, Prof. Dr., UMC Utrecht

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ACTUAL): June 1, 2016
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (ACTUAL): April 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2018
• Last Update Submitted That Met QC Criteria: March 29, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Inflammation; Infection; Pathologic Processes; Shock; ICU; Sepsis; Intensive Care; Systemic Inflammatory Response Syndrome; Wounds and Injuries; Neutrophils; PMN; polytrauma; Innate immunity; Multiple Organ Failure; Granulocytes; host-pathogen
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Shock; Multiple Trauma; Multiple Organ Failure
• Other Study ID Numbers: 43279

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO