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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hemorrhagic Shock, Traumatic Injury

Intervention / Treatment
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* Biological: low titer whole blood
* Biological: Standard Care


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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole Blood<br>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<br>* 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<br>|
| Active Comparator: Standard Care<br>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<br>* crystalloid infusion or blood component transfusion resuscitation<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemorrhage, trauma, whole blood