Longitudinal Gene Expression Profiling in Adults After Traumatic Injury
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease, Hospital |
| Therapuetic Areas: | Immunology / Infectious Diseases, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/31/2019 |
| Start Date: | January 2016 |
| End Date: | August 2017 |
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.
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.
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.
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.
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.
We found this trial at
2
sites
Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
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