Longitudinal Gene Expression Profiling in Adults After Traumatic Injury

Sepsis Clinical Trial

Official title:

Longitudinal Gene Expression Profiling in Adults After Traumatic Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02656459
• Other study ID #: IRB-35447
• Status: Completed
• Start date: January 2016
• Est. completion date: August 2017

Study information

• Verified date: March 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: August 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infection
• Sepsis
• Trauma
• Wounds and Injuries

Intervention

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

Locations

Country	Name	City	State
Germany	University Hospital Essen	Essen
Germany	University of Gottigen	Gottingen
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	University Medical Center Goettingen

Countries where clinical trial is conducted

United States,  Germany, 

References & Publications (2)

Sweeney TE, Khatri P. Comprehensive Validation of the FAIM3:PLAC8 Ratio in Time-matched Public Gene Expression Data. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1260-1. doi: 10.1164/rccm.201507-1321LE. — View Citation

Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015 May 13;7(287):287ra71. doi: 10.1126/scitranslmed.aaa5993. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	11-gene set / Sepsis MetaScore	Time-matched controls are necessary to prevent bias due to changes over time that occur with recovery from injury.	Patients with infections will be compared to time-matched patients without infections (+/- 24 hours).