Validation of a Genomics Based Prognostic in Severe Trauma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Time to recovery from organ injury.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: 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.
干预措施: Healthy Volunteers (Other)
结局指标
主要结局
Time to recovery from organ injury.
时间窗: 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
时间窗: 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.
次要结局
- Ventilator-free days(Baseline admission to the hospital through day 28 of the study.)
- 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.)
- 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.)
- Total IV fluids received.(At baseline through the first 24 hours of admission to the 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.)
- Telephone Interview and Rand 36-Item Health Survey(Post hospital discharge at 4 months (+/- 60 days) and at 12 months (+/- 90 days))