Completed Research

The Center for Translational Injury Research (CeTIR) at UTHealth Houston has conducted several significant studies to improve trauma care. These completed studies have provided valuable insights and helped move the field forward with evidence-based practices. Below are the details of these completed studies.

• A Multi-Center, Randomized, Controlled Trial Evaluating the Effects of Early High-Dose Cryoprecipitate in Adult Patients with Major Trauma Hemorrhage Protocol Activation (Cryostat2 Study)

  A Multi-Center, Randomized, Controlled Trial Evaluating the Effects of Early High-Dose Cryoprecipitate in Adult Patients with Major Trauma Hemorrhage Protocol Activation (Cryostat2 Study)
  Site PI – Bryan Cotton, MD
  Co-Investigators – Erin Fox, PhD; Charles Wade, PhD
  Supporting Agency – Queen Mary University of London
  Bleeding is a major cause of death in severely injured patients. Many of these patients rapidly develop an abnormality of the clotting system, known as ‘acute traumatic coagulopathy’ (ATC). The two most important abnormalities in ATC are a low fibrinogen and increased clot breakdown. It has been hypothesized, and there are some non-randomized studies that show, that treatment of trauma patients who are bleeding with fibrinogen therapy stops bleeding more effectively than standard care, reduces transfusion needs and may reduce death rates. This study will look at the effects of transfusing early high dose cryoprecipitate (which is a concentrated source of fibrinogen), to adult trauma patients with severe bleeding within 90 minutes of admission to hospital. This study will evaluate whether early cryoprecipitate reduces death rates when major bleeding occurs after injury.

• Dronabinol on the Pain Experience (DOPE): a pragmatic, randomized clinical trial

  Dronabinol on the Pain Experience (DOPE): a pragmatic, randomized clinical trial
  PI – Krislynn Mueck, MD
  Co-Investigator – John Harvin, MD
  Supporting Agency – Eastern Association for the Surgery of Trauma (EAST)
  The opioid epidemic is an ongoing public health crisis that has only intensified during the COVID-19 pandemic. Due to the nature of multisystem injuries, need for multiple painful procedures, and lengthy hospitalization, injured patients’ acute pain control needs differ from those in other surgical specialties. In an effort to reduce opioid exposure while maintaining optimal pain control, surgeons are increasingly using multi-modal pain regimens (MMPR). Our current institutional MMPR is derived from the Multi-Modal Analgesic Strategy for Trauma (MAST) trial which demonstrated a reduction in opioid exposure while maintaining pain control. However, adjunct medications are commonly added to improve pain control. One such adjunct is dronabinol, a synthetic delta-9-tetrahydrocannabinol (delta-9-THC), that is commonly used for its analgesic properties but the data supporting its use for acute pain after traumatic injury is limited. Aim 1: To perform a randomized comparative effectiveness trial to identify the effect dronabinol has on opioid exposure when used as an adjunct to our current institutional MMPR. Aim 2: To examine the effect dronabinol has on opioid exposure when used as an adjunct to our current institutional MMPR in known high risks groups such as patients with a positive urine drug screen.

• LITES Task Order 4: Cold-Stored Platelet Early Intervention in Hemorrhagic Shock Trial (CriSP-HS)

  LITES Task Order 4: Cold-Stored Platelet Early Intervention in Hemorrhagic Shock Trial (CriSP-HS)
  Site PI – Bryan Cotton, MD
  Co-Investigator – Erin Fox, PhD
  Supporting Agency – University of Pittsburgh
  Resuscitation strategies for the acutely injured patient in hemorrhagic shock have evolved with patients benefitting from receiving less crystalloid and early red blood cell use with balanced ratios of plasma and platelets. These resuscitation practices have been termed Damage Control Resuscitation and have been incorporated into massive transfusion protocols in level 1 trauma centers across the country. Despite these changes, deaths from traumatic hemorrhage continue to occur in the first hours following arrival at the trauma center, underscoring the importance of early interventions which provide benefit. Platelet transfusions are a vital component of damage control resuscitation and are essential to early hemostasis. Currently, platelets are not available in the prehospital or early resuscitation setting and are typically provided only after massive transfusion protocols are initiated, beyond the early phase of care for hemorrhagic shock patients. Platelet use in far forward environments are not available due to logistical storage and shelf-life requirements. Cold-stored platelets can be refrigerated similar to red blood cells and plasma units and may be less prone to bacterial contamination. Growing evidence suggests that cold-stored platelets have superior hemostatic capabilities. For patients in hemorrhagic shock, cold stored platelets may be beneficial in an urgent release fashion soon after arrival to the trauma center as compared to current standard care. The aims of the Cold Stored Platelet early intervention (CriSP) pilot trial are to determine the feasibility, efficacy and safety of urgent release cold stored platelets in patients in hemorrhagic shock.
  AIM 1: Determine the feasibility, most appropriate study population and primary outcome that will lead to a large multicenter clinical trial designed to evaluate the effectiveness of cold stored platelet early intervention in patients with injury and hemorrhagic shock. AIM 2: Determine whether early cold stored platelet infusion compared to standard care results in improved clinical outcomes and hemostatic function in injured patients with hemorrhagic shock. AIM 3: Determine if early cold stored platelet hemostatic function is similar at 1 through 7 days as compared to 8 through 14 days in patients with hemorrhagic shock. CriSP-HS Trial

• Mesenchymal Stem Cells for Treatment of ARDS Following Trauma

  Mesenchymal Stem Cells for Treatment of ARDS Following Trauma
  Site PI – Laura Moore, MD
  Co-Investigators – Charles Cox, MD; Erin Fox, PhD; Lillian Kao, MD; Charles Wade, PhD
  Supporting Agency – Regents of the University of California-San Francisco
  W81XWH-16-PRMRP-CTA – US Army Medical Research Acquisition Activity
  Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition in which the lung is injured or inflamed to the degree that it cannot properly exchange gases and oxygenate the body. ARDS can be caused by a variety of conditions including infections, trauma, severe blood loss, multiple or large volume blood transfusions, burns, and the inhalation of chemical poisons or smoke. According to the National Heart Lung and Blood Institute, approximately 190,000 people in the U.S. develop ARDS each year. Even with state-of-the-art supportive care with optimal, lung protective mechanical ventilation, the death rate from ARDS ranges from 25–40%, with higher rates seen in less technologically developed areas. Recent studies from the Department of Defense Iraq Trauma Registry (DoDTR) reported that ARDS developed in a large number of severely wounded warfighters and was associated with higher death rates. To date, there have been few advances in the treatment of major trauma related conditions such as ARDS. The development of new therapeutics that can limit the severity and/or progression of lung injuries that lead to ARDS and death is an immediate clinical need in both military and civilian sectors. The overall objective of this project is to carry out a randomized, double-blinded, placebo-controlled, multicenter phase 2b trial to test the therapeutic potential of allogeneic bone-marrow derived mesenchymal stromal cells (MSC) for treating ARDS in trauma patients.
  Aim 1: Test the clinical efficacy of intravenously delivered allogenic human MSCs in trauma patients with ARDS. Aim 2: Test the mechanisms by which MSCs reduce acute lung injury in trauma patients with ARDS.

• Microvascular Barrier Biomarkers to Predict ICP Therapeutic Intensity After Severe TBI

  Microvascular Barrier Biomarkers to Predict ICP Therapeutic Intensity After Severe TBI
  PI - Charles Cox, MD
  Co-Investigators – Erin Fox, PhD; Charles Wade, PhD
  Supporting Agency – US Army Medical Research & Material Command (W81XWH18SBAA1)
  Severe traumatic brain injury (TBI) is a leading cause of death and disability, and often occurs at the same time as multiple other injuries and with and without bleeding. Current care of the patient with a brain injury is designed to avoid factors that cause the initial injury to become worse (low blood pressure and lack of oxygen). This project seeks to identify early laboratory measures that can predict whether a patient is likely to get worse, then treat the causes of the condition. The ultimate goal is to be able to use a simple blood test that identifies the degraded components in the brain to rapidly identify the subset of severe TBI patients that require high-intensity neurocritical care.
  Aim 1: Determine the time course of syndecan-1 release and colloid osmotic pressure (COP) in patients with severe TBI, and correlate this with pressure-time intracranial hypertension (ICH) exposure. Aim 2: Test whether the degree of microvascular barrier disruption as quantified by initial or 24-hour peak endotheliopathy of trauma (EoT) results predicts the malignant intracranial pressure (ICP) phenotype.

• Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR)

  Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR)
  PROPPR was a randomized trial to evaluate ratios, massive transfusion patients receive either 1:1:1 (higher ratio) or a 1:1:2 (lower ratio) RBC:Plasma: Platelet with primary outcome of survival, and also complications and length of hospital stay. PROPPR Trial
  Conclusions & Relevance – Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.
  Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial

• Prehospital Resuscitation on Helicopter Study  (PROHS)

  Prehospital Resuscitation on Helicopter Study (PROHS)
  Background – Earlier us of in-hospital plasma platelets and red blood cells (RBCs) has improved survival in trauma patients with severe hemorrhage. Retrospective studies have associated improved early survival with prehospital blood product transfusion (PHT). The hypothesis of this study was that patients with severe traumatic injuries evacuated to level 1 trauma centers on air ambulances who received prehospital red blood cells and/or plasma would have lower in-hospital mortality compared to patients transferred by air ambulance who received only crystalloid. PROHS Trial
  Conclusion - Because of the unexpected imbalance in systolic blood pressure, Glasgow Coma Scale (GCS) and injury severity score (ISS) between systems with and without blood products on helicopters, matching was limited and the results of this study are inconclusive. With few units transfused to each patient and small outcome differences between groups, it is likely large, multicenter, randomized studies will be required to detect survival differences in this important population.
  Multicenter observational prehospital resuscitation on helicopter study

• Prospective, Observational, Multi-Center Major Trauma Transfusion Study (PROMMTT)

  Prospective, Observational, Multi-Center Major Trauma Transfusion Study (PROMMTT)
  Objective – To relate in-hospital mortality to early transfusion of plasma and/or platelets to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios.
  Conclusions – Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission.  Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.
  The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks