Type O Whole Blood and Assessment of Age During Prehospital Resuscitation Trial (TOWAR)

Type O Whole Blood and Assessment of Age During Prehospital Resuscitation (TOWAR) Trial

Open label, multi-center, pre-hospital randomized trial utilizing 10 level-1 trauma centers designed to determine the efficacy and safety of low titer whole blood resuscitation as compared to standard of care resuscitation in patients at risk of hemorrhagic shock and to appropriately characterize the hemostatic competency of whole blood relative to its age.

Study Overview

• Status: Recruiting
• Conditions: Hemorrhagic Shock; Traumatic Injury
• Intervention / Treatment: Biological: low titer whole blood; Biological: Standard Care

• Study Type: Interventional
• Enrollment (Estimated): 1020
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jason Sperry, MD; Phone Number: 412-802-8270; Email: sperryjl@upmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Not yet recruiting
      • University of Alabama at Birmingham
      • Contact: Joel Rodgers; Email: jrodgers@uabmc.edu
      • Principal Investigator: Mohammad Zain Hashmi, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • Recruiting
      • University of Louisville
      • Contact: Brian Harbrecht; Email: briang.harbrecht@louisville.edu
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • University of Mississippi Medical Center (UMMC)
      • Contact: Matthew Kutcher, MD; Phone Number: 601-815-1312; Email: mkutcher@umc.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinatti
      • Contact: Michael Goodman, MD; Phone Number: 513-558-5661; Email: goodmamd@ucmail.uc.edu
    • Cleveland, Ohio, United States, 44109
      • Recruiting
      • MetroHealth Systems
      • Contact: Jeffrey Claridge; Phone Number: 216-778-4684; Email: jclaridge@metrohealth.org
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Jason L Sperry, MD,MPH; Phone Number: 412-647-3065; Email: sperryjl@upmd.edu
      • Principal Investigator: Jason L Sperry, MD,MPH
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center
      • Contact: Brian Daley, MD; Phone Number: 865-251-4685; Email: bdaley@utmck.edu
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Mayur Patel, MD; Phone Number: 615-936-0083; Email: mayur.b.patel@vumc.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas Health Science Center at Houston
      • Contact: Bryan Cotton; Phone Number: 713-500-7313; Email: Bryan.A.Cotton@uth.tmc.edu
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • University of Washington
      • Contact: Richard Utarnachitt, MD, MS; Phone Number: 206-744-8468; Email: rutarnac@uw.edu
      • Principal Investigator: Richard Utarnachitt, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1.) Injured patients at risk of hemorrhagic shock being transported from scene or referral hospital to a participating TOWAR trial site that meet requirements for initiation of blood or blood component transfusion

AND

2A.) Systolic blood pressure ≤ 90mmHg and tachycardia (HR ≥ 108) at scene, at outside hospital or during transport OR

2B.) Systolic blood pressure ≤ 70mmHg at scene, at outside hospital or during transport

Exclusion Criteria:

1. Wearing NO TOWAR opt-out bracelet
2. Age > 90 or < 18 years of age
3. Isolated fall from standing injury mechanism
4. Known prisoner or known pregnancy
5. Traumatic arrest with > 5 minutes of CPR without return of vital signs
6. Brain matter exposed or penetrating brain injury (GSW)
7. Isolated drowning or hanging victims
8. Objection to study voiced by subject or family member at the scene
9. Inability to obtain IV or intraosseous access
10. Isolated burns without evidence of traumatic injury

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole Blood; Subjects will receive up to two units of whole blood as collected by local blood bank procedures and stored at 1-6 degrees Celsius initiated in the prehospital phase of care.	Biological: low titer whole blood; low titer whole blood, group O kept to either 21 days or 35 days based upon which preservation process is employed at each respective participating site
Active Comparator: Standard Care; Subjects will receive prehospital crystalloid infusion or blood component transfusion resuscitation per site standard care for the respective Emergency Medical unit/service.	Biological: Standard Care; crystalloid infusion or blood component transfusion resuscitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day mortality	All cause mortality within 30 days	Enrollment through 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of whole blood	Age of units of whole blood in days categorized into young (1-14 days) and old (>14 days) and compared across primary and secondary outcomes	During Procedure
3-hour mortality	Death within 3 hours of enrollment	Enrollment through 3 hours
6-hour mortality	Death within 6 hours of enrollment	Enrollment through 6 hours
24-hour mortality	Death within 24 hours of enrollment	Enrollment through 24 hours
In-hospital mortality	Death prior to hospital discharge	Enrollment through hospital discharge or 30 days
Time to death	Time in days from enrollment to death	Enrollment through death or 30 days
Blood and blood component transfusion type	Type of blood or blood component required for transfusion	Enrollment through 24 hours
Blood and blood component transfusion amount	Number of units of blood or blood component transfused	Enrollment through 24 hours
Time to blood and blood component transfusion	Amount of time from enrollment to transfusion of blood or blood component	Enrollment time to first transfusion
Multiple Organ Failure (MOF)	Organ dysfunction will be evaluated via the Denver Post-injury Multiple Organ Failure Score. Patients who are never admitted to the Intensive Care Unit (ICU) or those with a length of ICU stay of less than 48 hours will be considered to have a Denver score of 0. A summary of the Denver score may be calculated by summing the worst scores of each of the individual systems over the course of the ICU stay. A summary Denver score > 3 will be classified as MOF.	Enrollment through 7 days or ICU discharge
Hospital-acquired pneumonia	Pneumonia acquired during hospitalization per Center for Disease Control (CDC) criteria	Number of participants who develop pneumonia through 30 days
blood stream infection	Blood stream infection during hospitalization per CDC criteria	Number of participants who develop blood stream infection through 30 days
Acute Respiratory Distress Syndrome (ARDS)	The Berlin definition for mild ARDS (PaO2/FIO2, ≤ 300 mm Hg + timing, imaging and origin criteria) will be utilized as a threshold value to determine the incidence of ARDS and will be further stratified into Moderate (PaO2/FIO2, ≤ 200 mm Hg) and Severe (PaO2/FIO2, ≤ 100 mm Hg).	Number of participants who develop ARDS through 30 days
Prothrombin Time (PT)	Measurement of platelet hemostatic function	Enrollment through 60 minutes and 24 hours
International Normalized Ratio (INR)	Measurement of platelet hemostatic function	Enrollment through 60 minutes and 24 hours
Incidence of coagulopathy by rapid thrombelastography (rTEG)	Coagulopathy as indicated by rTEG measures	Enrollment through 60 minutes and 24 hours
rTEG platelet function	rTEG measurement of platelet hemostatic function	Enrollment through 60 minutes and 24 hours
Time to hemostasis	Ability to reach nadir transfusion requirement of 1 unit of red blood cells in a 60-minute time period in the first 4 hours following arrival	Enrollment through 4 hours
Transfusion reaction	Any transfusion complication	Enrollment through 24 hours
whole blood aggregometry	platelet function test using low-dose collagen as a stimulus	Enrollment through 60 minutes

Collaborators and Investigators

• Sponsor: Jason Sperry
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Jason L Sperry, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: December 23, 2020
• First Posted (Actual): December 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: trauma; hemorrhage; whole blood
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Shock; Wounds and Injuries; Shock, Hemorrhagic
• Other Study ID Numbers: STUDY20110430; W81XWH-16-D-0024 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be shared with the funding agency as well as other researchers upon request to the Principal Investigator.
• IPD Sharing Time Frame: Data will become available after publication of the primary manuscript.
• IPD Sharing Access Criteria: Requests for data will be submitted in writing and reviewed by the Principal Investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No