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

• ClinicalTrials.gov Identifier: NCT03489577
• Recruitment Status: Terminated
• First Posted: April 5, 2018
• Last Update Posted: April 5, 2018
• Sponsor: UMC Utrecht
• Information provided by (Responsible Party): Prof. dr Leenen, UMC Utrecht

Study Description

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.

Condition or disease
Multiple Trauma; Sepsis; Innate Immune Response; Disorder of Neutrophils; Multiple Organ Dysfunction Syndrome

Study Design

• Study Type: Observational
• Actual Enrollment: 15 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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 Start Date: June 2014
• Actual Primary Completion Date: June 1, 2016
• Actual Study Completion Date: June 1, 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Bactericidal capacity of neutrophils and sepsis [ Time Frame: 15 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 :

1. Bactericidal capacity of neutrophils and infectious complications [ Time Frame: 15 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)
2. Bactericidal capacity of neutrophils and pro-inflammatory complications [ Time Frame: 15 days following admission to the ICU ]
   The correlation between bactericidal function of neutrophils and the occurrence of pro-inflammatory complications (SIRS).
3. Priming capacity of neutrophils and infectious complications [ Time Frame: 15 days following admission on the ICU ]
   The relationship between the responsiveness of neutrophils to a priming stimulus (fMLP) and the occurrence of infectious complications
4. Complement system and infectious complications [ Time Frame: 15 days following admission to the ICU ]
   The correlation between functionality of the complement system and the occurence of infectious complications.
5. T-cell proliferation and infectious complications [ Time Frame: 15 days following admission on ICU ]
   The difference in suppression of T-cell proliferation in patients suffering infectious complications versus non-infectious patients.

Biospecimen Retention:   Samples Without DNA

Blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

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

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

Contacts and Locations

Locations

Netherlands

University Medical Center Utrecht

Utrecht, Netherlands, 3508 GA

Sponsors and Collaborators

UMC Utrecht

Investigators

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

More Information

• Responsible Party: Prof. dr Leenen, Prof. Dr., UMC Utrecht
• ClinicalTrials.gov Identifier: NCT03489577
• Other Study ID Numbers: 43279
• First Posted: April 5, 2018
• Last Update Posted: April 5, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Prof. dr Leenen, UMC Utrecht:

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

Additional relevant MeSH terms:

Multiple Organ Failure; Multiple Trauma; Pathologic Processes; Wounds and Injuries; Shock