A Validation of a Genomics Based Prognostic in Severe Trauma

NCT01810328 | Completed

• 3 other identifiers: IRB201601501-NR01GM104481-01482-2012
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

Conditions

Trauma; Complications; Multiple Organ Failure

Outcome Measures

Primary Outcomes (2)

• Genomic score

  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.

  Assement at the first 12 and 24 hours of hospitalization.

• Time to recovery from organ injury.

  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.

  Change in baseline through day 28 of the study.

Secondary Outcomes (16)

• Mechanism of injury

  Evaluated at the time of injury, information taken at baseline admission to emergency room.

• Initial hemodynamic variables

  At baseline admission to emergency room.

• Injury Severity Score

  Obtained within 6 months following discharge from hospital.

• Patient demographics

  Done at baseline admission to hospital.

• Time to definitive care

  At baseline through the first 12 hours of admission to the hospital.

Other Outcomes (2)

• Nosocomial Infection

  Baseline admission to the hospital through day 28 of the study.

• Resource Utilization and Mortality

  Baseline admission to the hospital through day 28 in the study.

Study Arms (2)

Traumatized population

ACTIVE COMPARATOR

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

Healthy Volunteers

ACTIVE COMPARATOR

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

Interventions

Traumatized population OTHER

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.

Traumatized population

Healthy Volunteers OTHER

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.

Healthy Volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator
• Massachusetts General Hospital: collaborator

Study Sites (2)

UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF

Gainesville, Florida, 32610, United States

Location

UW Harborview Research and Training Building

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• Brakenridge SC, Wang Z, Cox M, Raymond S, Hawkins R, Darden D, Ghita G, Brumback B, Cuschieri J, Maier RV, Moore FA, Mohr AM, Efron PA, Moldawer LL. Distinct immunologic endotypes are associated with clinical trajectory after severe blunt trauma and hemorrhagic shock. J Trauma Acute Care Surg. 2021 Feb 1;90(2):257-267. doi: 10.1097/TA.0000000000003029.

  PMID: 33214489 DERIVED

• Mira JC, Cuschieri J, Ozrazgat-Baslanti T, Wang Z, Ghita GL, Loftus TJ, Stortz JA, Raymond SL, Lanz JD, Hennessy LV, Brumback B, Efron PA, Baker HV, Moore FA, Maier RV, Moldawer LL, Brakenridge SC. The Epidemiology of Chronic Critical Illness After Severe Traumatic Injury at Two Level-One Trauma Centers. Crit Care Med. 2017 Dec;45(12):1989-1996. doi: 10.1097/CCM.0000000000002697.

  PMID: 28837430 DERIVED

MeSH Terms

Conditions

Wounds and Injuries; Multiple Organ Failure

Condition Hierarchy (Ancestors)

Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lyle L Moldawer, Ph.D.

  University of Florida

  PRINCIPAL INVESTIGATOR

• Ronald Maier, M.D.

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 13, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: July 23, 2019
• Last Updated: July 24, 2019

Record last verified: 2019-07

Locations

US (2)