A Validation of a Genomics Based Prognostic in Severe Trauma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Florida
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01810328
First received: March 11, 2013
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Trauma; Complications
Multiple Organ Failure
Other: Traumatized population
Other: Healthy Volunteers

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Validation of a Genomics Based Prognostic in Severe Trauma

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Genomic score [ Time Frame: Assement at the first 12 and 24 hours of hospitalization. ] [ Designated as safety issue: No ]
    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.

  • Time to recovery from organ injury. [ Time Frame: Change in baseline through day 28 of the study. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mechanism of injury [ Time Frame: Evaluated at the time of injury, information taken at baseline admission to emergency room. ] [ Designated as safety issue: No ]
    The circumstance in which an injury occurs, for example: sudden deceleration, wounding by a projectile, or crushing by a heavy object.

  • Initial hemodynamic variables [ Time Frame: At baseline admission to emergency room. ] [ Designated as safety issue: No ]
    The first hemodynamic variables available following patient's admission to hospital.

  • Injury Severity Score [ Time Frame: Obtained within 6 months following discharge from hospital. ] [ Designated as safety issue: No ]
    The Injury Severity Score (ISS) is an anatomical scoring system that provides an overall score for patients with multiple injuries. Each injury is assigned an Abbreviated Injury Scale (AIS) score and is allocated to one of six body regions (Head, Face, Chest, Abdomen, Extremities(including Pelvis), External). Only the highest AIS score in each body region is used. The 3 most severely injured body regions have their score squared and added together to produce the ISS score. The ISS score takes values from 0 to 75.

  • Patient demographics [ Time Frame: Done at baseline admission to hospital. ] [ Designated as safety issue: No ]
    The patient's age, sex, race, ethnicity, height, weight, and BMI.

  • Time to definitive care [ Time Frame: At baseline through the first 12 hours of admission to the hospital. ] [ Designated as safety issue: No ]
  • Total IV fluids received. [ Time Frame: At baseline through the first 24 hours of admission to the hospital. ] [ Designated as safety issue: No ]
  • Type of IV fluids received [ Time Frame: At baseline through the first 24 hours of admission to the hospital. ] [ Designated as safety issue: No ]
    Crystalloids and Colloids are considered IV fluids.

  • Plasma cytokines measured at time point number one [ Time Frame: At baseline through the first 12 hours of admission to the hospital. ] [ Designated as safety issue: No ]
    Plasma cytokines will be measured by Luminex. The following cytokines will be determined: IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐15, IL‐18, IL‐23, GM‐CSF, G‐CSF, SDF‐1, IP‐10 (CXCL10), MCP‐1, SDF‐1 (CXCL12) and ckitL.

  • Plasma cytokines measured at time point number two. [ Time Frame: Change in 12 hour to hour 24 after admission to the hospital. ] [ Designated as safety issue: No ]
    Plasma cytokines will be measured by Luminex™. The following cytokines will be determined: IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐15, IL‐18, IL‐23, GM‐CSF, G‐CSF, SDF‐1, IP‐10 (CXCL10), MCP‐1, SDF‐1 (CXCL12) and ckitL.

  • Overall incidence of ARDS [ Time Frame: 48 hours after admission to the hospital through day 28 of the study. ] [ Designated as safety issue: No ]
    ARDS will be defined strictly based on the American‐European Consensus Conference on ARDS published in 1994. Acute Lung Injury (ALI), a milder form of ARDS, will also be evaluated using the same clinical criteria except for a PaO2/FiO2 <300. The clinical research nurse will identify the development of ARDS and ALI by daily screening of the patients for these clinical criteria beginning 48 hours following injury.

  • Overall incidence of Multiple Organ Failure [ Time Frame: 48 hours after admission to hospital through day 28 of the study. ] [ Designated as safety issue: No ]

    The development of additional organ dysfunction will be tracked by the well validated MOF Score (MOFScore). Its continuous nature allows detection of subtle differences in organ dysfunction not identified by dichotomous measures. The MOFscore assigns points to each of the six organ systems indicated and the summary score is calculated by summing the worst scores of each organ system over the course of the ICU stay. Because the MOFScore is designed to measure stable alterations in organ function, the first 48 hours post‐injury are excluded. Those who die in first 48 hrs will be assigned the maximum MOF score of 24, and those who are discharged before 48 hrs will have a MOF score of 0.

    A score of 6 or greater will be considered MOF.


  • Mortality [ Time Frame: Baseline through day 28 of the study. ] [ Designated as safety issue: No ]
    28 day mortality

  • Survival to hospital discharge. [ Time Frame: Baseline admission to the hospital through discharge from the hospital. ] [ Designated as safety issue: No ]
  • Duration of hospital ICU stay [ Time Frame: Baseline admission to the hospital through the last day in ICU. ] [ Designated as safety issue: No ]
  • Ventilator-free days [ Time Frame: Baseline admission to the hospital through day 28 of the study. ] [ Designated as safety issue: No ]
  • Telephone Interview and Rand 36-Item Health Survey [ Time Frame: Post hospital discharge at 4 months (+/- 60 days) and at 12 months (+/- 90 days) ] [ Designated as safety issue: No ]
    After discharge from the hospital for the trauma population, we will perform two post discharge telephone interviews to assess subject health and recovery. The first at 4 months (+/- 60 days) and the second at 12 months (+/- 90 days). The interviews will consist of a short questionnaire and the Rand 36-Item Health Survey 1.0.


Other Outcome Measures:
  • Nosocomial Infection [ Time Frame: Baseline admission to the hospital through day 28 of the study. ] [ Designated as safety issue: No ]
    Central line-associated bloodstream infections, catheter-associated urinary tract infections, and ventilator-associated pneumonia. Infections may also occur at surgery sites, known as surgical site infections. Additionally, Clostridium difficile can cause gastrointestinal infection; patients can be exposed to this bacterium through contaminated surfaces or the spores can be transferred on unclean hands of others.

  • Resource Utilization and Mortality [ Time Frame: Baseline admission to the hospital through day 28 in the study. ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: October 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Other: 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.
Active Comparator: 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.
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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:

  1. all adults (age ≥18)
  2. Ability to obtain Informed Consent prior to blood collection.

Exclusion Criteria Healthy Volunteers:

  1. Severe pre-existing organ dysfunction
  2. Subjects who have received oncolytics within 14 days
  3. Subjects who are HIV + and have a CD4 count of <200/mm3
  4. Subjects not expected to survive 28 days due to pre-existing, uncorrectable medical condition
  5. Total body surface burns >40%
  6. Prisoners
  7. Current, chronic steroid use
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01810328

Contacts
Contact: Jennifer D Lanz, ARNP, MSN 352-273-5497 jennifer.lanz@surgery.ufl.edu
Contact: Ruth J Davis, RN 352-273-8759 ruth.davis@surgery.ufl.edu

Locations
United States, Florida
UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF Recruiting
Gainesville, Florida, United States, 32610
Principal Investigator: Lyle L Moldawer, Ph. D.         
United States, Washington
UW Harborview Research and Training Building Recruiting
Seattle, Washington, United States, 98104
Contact: Laura Hennessy, RN    206-744-7723    hennessy@uw.edu   
Principal Investigator: Ronald Maier, M.D.         
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Lyle L Moldawer, Ph.D. University of Florida
Principal Investigator: Ronald Maier, M.D. University of Washington
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01810328     History of Changes
Other Study ID Numbers: 482-2012, R01GM104481-01
Study First Received: March 11, 2013
Last Updated: April 29, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Organ Failure
Wounds and Injuries
Shock
Pathologic Processes

ClinicalTrials.gov processed this record on July 28, 2014