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

Terminated
Conditions
Multiple Trauma
Sepsis
Disorder of Neutrophils
Multiple Organ Dysfunction Syndrome
Innate Immune Response
Registration Number
NCT03489577
Lead Sponsor
UMC Utrecht
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
15
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Bactericidal capacity of neutrophils and sepsis15 days following admission on ICU

The correlation between reduced bactericidal capacity of neutrophils acquired from severely injured patients and the late occurrence of sepsis

Secondary Outcome Measures
NameTimeMethod
Bactericidal capacity of neutrophils and pro-inflammatory complications15 days following admission to the ICU

The correlation between bactericidal function of neutrophils and the occurrence of pro-inflammatory complications (SIRS).

Bactericidal capacity of neutrophils and infectious complications15 days following admission to the ICU

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)

T-cell proliferation and infectious complications15 days following admission on ICU

The difference in suppression of T-cell proliferation in patients suffering infectious complications versus non-infectious patients.

Priming capacity of neutrophils and infectious complications15 days following admission on the ICU

The relationship between the responsiveness of neutrophils to a priming stimulus (fMLP) and the occurrence of infectious complications

Complement system and infectious complications15 days following admission to the ICU

The correlation between functionality of the complement system and the occurence of infectious complications.

Trial Locations

Locations (1)

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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