Longitudinal Gene Expression Profiling in Adults After Traumatic Injury

The purpose of this study is to examine the immune response to traumatic injury and subsequent infections in critically ill adults. Traumatic injuries lead to severe dysregulation of the immune system, and predispose to severe infections. Diagnosing these infections in a timely manner is paramount in reducing morbidity and mortality, but diagnosis is made difficult by the inflammatory response to trauma. The main purpose of the study is to prospectively test the diagnostic power of the expression of an 11-gene set which the investigators recently published (Sweeney et al., Sci Transl Med, 2015). Since the timing of an acquired infection cannot be determined a priori, this study is designed to be a longitudinal examination of a cohort of traumatically injured adults. The investigators will draw blood at regular intervals, as well as at day of diagnosis of infection for any patient that are diagnosed with an infection. The investigators will then assay the blood for gene expression levels post hoc, and correlate the molecular profiles with clinical information to establish a prospective estimate of diagnostic power.

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Key information

Conditions

Sepsis Infection Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Systemic Inflammatory Response Syndrome Trauma Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University Hospital Essen, Essen, Germany

About this study

Consecutive patients who meet criteria (see below) will be enrolled. Whole blood will be drawn and stored in PAXgene tubes. Blood will be drawn within 24 hours of ICU admission (ICU day 1), and then every three days subsequently (ICU days 4, 7, 10, 13) for two weeks. In addition, a tube of blood will be drawn at the time of clinical diagnosis of infection, if an infection is diagnosed (see below). Patients who are discharged from the ICU prior to two weeks will no longer be profiled. The hour and date of admission, and the hour and date of each subsequent blood draw, will be recorded.

Rates of hospital-acquired infection after severe traumatic injury run around 30-50%. The investigators will enroll 50 patients, which should net around 20 patients with infections, and 30 time-matched non-infected controls. In total, an average of 4 samples/patient, or 200 total blood samples, are expected.

Diagnosis of Infection:

The main purpose of the study is to examine gene expression response to infections. As a result, careful attention must be paid to how infections are classified. First, two systemic inflammatory reaction syndrome (SIRS) criteria are NOT necessary to be designated as infected. Second, the time of diagnosis of infection (and the time of extra blood sampling) will be the time of clinical diagnosis, not the later time that cultures turn positive. It will thus be based on clinical judgement. Finally, post-hoc criteria for infections are described elsewhere. Patients need to eventually meet these criteria to be counted as infected; this will be done in the analysis phase, not the clinical phase.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Consecutive adults (>=18 years old) admitted to the ICU after blunt traumatic injury.

Exclusion criteria

Patients with isolated traumatic head or spinal cord injuries will not be included.
Furthermore, patients with prior or under continuous antibiotic therapy will be excluded (e.g. in case of intestinal perforation).
We will not exclude patients who are given <=24 hours of perioperative antibiotics.

Treatment and study plan

11-gene set

Other

This trial is NOT interventional. The 11-gene set / Sepsis MetaScore will be tested post-hoc.

Other names: Sepsis MetaScore

Primary outcomes

11-gene set / Sepsis MetaScore

Time frame: Patients with infections will be compared to time-matched patients without infections (+/- 24 hours).

Time-matched controls are necessary to prevent bias due to changes over time that occur with recovery from injury.

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Collaborators

University Medical Center Goettingen

Registry information

Important dates

Study start: 2016
Primary completion: 2017
Study completion: 2017
First posted: Jan 15, 2016
Registry last updated: Mar 29, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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