Clinical trial NCT03489577: The Role of Post-traumatic Inhibition of the Innate and Adaptive Immune System in the Development of Infectious Complications in Severely Injured Patients
Official title: The Role of Post-traumatic Inhibition of the Innate and Adaptive Immune System in the Development of Infectious Complications in Severely Injured Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Multiple Trauma
Sepsis
Innate Immune Response
Disorder of Neutrophils
Multiple Organ Dysfunction Syndrome
Keywords: Inflammation
Multiple Organ Failure
Sepsis
Wounds and Injuries
Pathologic Processes
Shock
Infection
Systemic Inflammatory Response Syndrome
Neutrophils
PMN
Granulocytes
Innate immunity
ICU
Intensive Care
polytrauma
host-pathogen
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2018-04-05
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Trauma patients likely to be admitted to the intensive care unit of the UMCU

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.


Eligibility criteria: 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

Primary outcomes:
measure: Bactericidal capacity of neutrophils and sepsis
timeFrame: 15 days following admission on ICU
Secondary outcomes:
measure: Bactericidal capacity of neutrophils and infectious complications
timeFrame: 15 days following admission to the ICU
measure: Bactericidal capacity of neutrophils and pro-inflammatory complications
timeFrame: 15 days following admission to the ICU
measure: Priming capacity of neutrophils and infectious complications
timeFrame: 15 days following admission on the ICU
measure: Complement system and infectious complications
timeFrame: 15 days following admission to the ICU
measure: T-cell proliferation and infectious complications
timeFrame: 15 days following admission on ICU
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Pieter Leliefeld, Md
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Luke PH Leenen, Prof. Dr.
role: STUDY_CHAIR
References: