Validation of a Genomics Based Prognostic in Severe Trauma
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Florida
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Time to recovery from organ injury.
Study Overview
Brief Summary
The purpose of this study is to learn more about how to treat patients with severe injuries related to trauma and to prevent failure of vital organs in this patient population. Approximately 200 severely injured patients with blunt trauma and 40 healthy volunteer subjects will be enrolled in this study. During the study seven blood samples (4-5 mls) will be collected from patients who have suffered severe trauma over a 28 day period. A one time 5 ml blood sample will be collected from the healthy volunteers. Clinical data will be collected daily while patients are hospitalized. The initial blood sample must be collected from qualifying patients within the first 12 hours of admission to the hospital. The reason for blood sampling is to validate a rapid genomic test in real time. Once confirmed, this genomic test can be used to identify patients who will have a complicated clinical course and would, therefore, be good candidates for interventional, immunomodulatory therapies.
Detailed Description
Specific Aim: To prospectively validate a rapid genomic test obtained from blood leukocyte subpopulation of severely traumatized patients in the first 24 hours after admission, that can be used to discriminate those patients who will have a complicated clinical trajectory and would, therefore, be good candidates for interventional, immunomodulatory therapies.
Following severe blunt traumatic injury and during recovery, alterations in the leukocyte transcriptome occur. Thus, we propose that a leukocyte transcriptome signal based on the expression of the validated 63 total leukocyte or 181 PMN genes can be used to identify patients who are at risk of a complicated clinical outcome, either alone or when combined with anatomical or physiological predictors. The goal of this clinical trial is to validate the predictive ability of this transcriptome-based prognostic.
This is a non-interventional, observational study of 200 severely injured patients with blunt trauma and 40 healthy volunteers. The entry criteria will be the same as has been used for the past eight years with the Glue Grant. Severe blunt injured patients that meet the inclusion criteria will undergo rapid leukocyte genomic screening at admission and the following morning(~24 hrs). Additional blood samples will be collected at 4, 7, 14, 21 and 28 days, or as long as the patients are in the trauma or surgical intensive care unit, for banking.
Over a four year period, we will enter 240 subjects from the University of Florida and from the University of Washington at Harborview Medical Center. In the trauma subjects, blood samples will be collected at admission, days 1, 4, 7, 14, 21 and 28, or until discharge from the ICU or death. A total of 4 to 5 mLs of blood will be collected at each time point. In the healthy volunteers, a one-time blood sample will be collected.
Screening and Consent: Trauma patients will be identified by study personnel following presentation to the emergency room. The subject or legal next-of-kin will be approached for consent within 96 hours if the patient meets entry criteria. We ask for delayed consent in this patient population for 96 hours due to the severity of the injuries, the vulnerable nature of the patient at this early time, and the challenge in reaching the patient's legal representatives. Should informed consent not be obtained within 96 hours, all blood samples and data collected will be discarded.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Trauma Patients:
- •All adults (age ≥18)
- •Blunt trauma patients with hemorrhagic shock, defined by either a systolic BP (SBP) <90 mm Hg or base deficit (BD) <-6 meq
- •Ability to obtain Informed Consent within 96 hours of injury.
- •Ability to obtain the first lab draw within 12 hours of presentation to the Emergency Department.
Exclusion Criteria
- •Trauma Patients:
- •Patients not expected to survive greater than 48 hours.
- •Patients with severe head injury.
- •Severe pre-existing organ dysfunction
- •Those that we are unable to obtain the first blood sample within 12 hours of injury
- •Subjects who have received oncolytics within 14 days
- •Subjects who are HIV + and have a CD4 count of <200/mm3
- •Subjects not expected to survive 28 days due to pre-existing, uncorrectable medical condition
- •Total body surface burns >40%
- •Prisoners
- •Current, chronic steroid use
- •If it is uncertain what the patient's past medical history is at the time of enrollment, they can be enrolled in the study and subsequently removed if they fail to meet criteria. This will be done because there are many circumstances with this patient population due to the severity of the injuries, the vulnerable nature of the patient at this early time, and the challenge in reaching the patient's legal representatives that we are unaware of their past medical history. The purpose of these exclusions is to ensure an adequate allocation of resources. Specifically, our goal is to evaluate patients at high risk for Multiple Organ Dysfunction Syndrome (MODS). Those with anticipated early death will add little to achieving this objective. Severe head injuries are excluded as well since the mortality in these subjects is usually attributable to their head injury rather than severe organ dysfunction. In addition, steroid use is known to affect the immunologic response to injury.
- •Inclusion Criteria Healthy Volunteers:
- •all adults (age ≥18)
- •Ability to obtain Informed Consent prior to blood collection.
- •Exclusion Criteria Healthy Volunteers:
- •Severe pre-existing organ dysfunction
- •Subjects who have received oncolytics within 14 days
- •Subjects who are HIV + and have a CD4 count of <200/mm3
- •Subjects not expected to survive 28 days due to pre-existing, uncorrectable medical condition
- •Total body surface burns >40%
- •Current, chronic steroid use
Arms & Interventions
Traumatized population
In the traumatized population (severe blunt traumatic injury), blood samples will be collected at admission, days 1, 4, 7, 14, 21 and 28, or until discharge from the ICU or death. A total of 5 mLs of blood will be collected at admission and day 1, 4 mLs of blood will be collected at each remaining time point.
Intervention: Traumatized population (Other)
Healthy Volunteers
The healthy volunteer participants will donate a one-time 5 mL blood sample which will undergo rapid leukocyte genomic screening. These controls will allow the investigators to determine if the values obtained are accurate, reliable, and repeatable.
Intervention: Healthy Volunteers (Other)
Outcomes
Primary Outcomes
Time to recovery from organ injury.
Time Frame: Change in baseline through day 28 of the study.
Time to recovery (TTR) is defined as the number of days in which the modified Marshall MODS score remains persistently above a score of zero. Designation of a "complicated outcome" is applied if the modified Marshall MODS score is above zero for greater than or equal to 14 days, or late death occurs. The designation of "other clinical outcome" will be a TTR less than 14 days.
Genomic score
Time Frame: Assement at the first 12 and 24 hours of hospitalization.
A genomic score will be derived and assessed for each patient from the first two blood collections. A threshold score will be generated prior to the study initiation that will be used to statistically assign patients to either a "complicated outcome" or "other outcome", with primary goal being to identify severe trauma patients who are likely to have a complicated clinical course.
Secondary Outcomes
- Total IV fluids received.(At baseline through the first 24 hours of admission to the hospital.)
- Telephone Interview and Rand 36-Item Health Survey(Post hospital discharge at 4 months (+/- 60 days) and at 12 months (+/- 90 days))
- Initial hemodynamic variables(At baseline admission to emergency room.)
- Patient demographics(Done at baseline admission to hospital.)
- Overall incidence of ARDS(48 hours after admission to the hospital through day 28 of the study.)
- Survival to hospital discharge.(Baseline admission to the hospital through discharge from the hospital.)
- Duration of hospital ICU stay(Baseline admission to the hospital through the last day in ICU.)
- Ventilator-free days(Baseline admission to the hospital through day 28 of the study.)
- Time to definitive care(At baseline through the first 12 hours of admission to the hospital.)
- Plasma cytokines measured at time point number two.(Change in 12 hour to hour 24 after admission to the hospital.)
- Overall incidence of Multiple Organ Failure(48 hours after admission to hospital through day 28 of the study.)
- Mechanism of injury(Evaluated at the time of injury, information taken at baseline admission to emergency room.)
- Injury Severity Score(Obtained within 6 months following discharge from hospital.)
- Plasma cytokines measured at time point number one(At baseline through the first 12 hours of admission to the hospital.)
- Type of IV fluids received(At baseline through the first 24 hours of admission to the hospital.)
- Mortality(Baseline through day 28 of the study.)