Pragmatic Prehospital Group O Whole Blood Early Resuscitation Trial

Study Overview
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Brief Summary
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Despite advances in trauma resuscitation, a paucity of therapeutic interventions are available early enough to reduce the downstream morbidity and mortality attributable to hemorrhage, shock and coagulopathy. Due to the time sensitive nature of the treatment of hemorrhage, the ideal resuscitation intervention would entail use of a blood product containing all essential hemostatic components, closest to time of injury, where prevention or reversal of the devastating downstream consequences of shock and coagulopathy can occur. This proposal will characterized the efficacy of whole blood resuscitation initiated in the prehospital setting to patients in hemorrhagic shock which represents this ideal intervention post-injury. These results will have great potential to dramatically change the way trauma resuscitation occurs today.

Detailed Description
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Traumatic injury represents an incredible health care burden in the United States and worldwide. Hemorrhage is estimated to be responsible for over 40% of all trauma-related deaths. Ongoing traumatic blood loss is complicated by the well-known 'lethal triad' of coagulopathy, hypothermia and acidosis which results in further unbridled hemorrhage. Uncontrolled bleeding, resultant shock and organ dysfunction remain the leading causes of early in-hospital mortality. Despite advances in trauma resuscitation, a paucity of therapeutic interventions are available early enough to reduce the downstream morbidity and mortality attributable to hemorrhage, shock and coagulopathy. In-hospital resuscitation of traumatic hemorrhage has changed over the past decade. The underlying principle of current resuscitation practice focuses on preventing or reversing the effects of coagulopathy with the early use of a balanced component transfusion strategy (1:1:1 - plasma: packed red blood cells: platelets). This reconstituted strategy has also been coined 'whole blood-like' resuscitation despite being inferior compositionally to whole blood. The use of whole blood was historically the gold standard for treating hemorrhagic shock during World War I and II, prior to sweeping changes in blood banking practice. Whole blood use continues today and is thought to provide the bleeding patient the identical components they are losing with maximal resuscitative and hemostatic effects. Recent military experiences continue to show the benefits of fresh whole blood resuscitation demonstrating significant survival and hemostatic advantages. Whole blood has also been postulated to improve microcirculatory hemodynamics, reduce the 'storage lesion' effect and minimize donor exposure risks. A recent civilian study has also demonstrated benefit using modified whole blood after arrival to the hospital where appropriate blood typing and cross matching was performed prior to transfusion. Due to the time sensitive nature of the treatment of hemorrhage, the ideal resuscitation intervention would entail use of a blood product containing all essential hemostatic components, closest to time of injury, where prevention or reversal of the devastating downstream consequences of shock and coagulopathy can occur. Initiation of whole blood resuscitation in the prehospital setting and continued through the in-hospital phase of treatment to patients in hemorrhagic shock represents this ideal intervention post-injury. Essential to the prehospital initiation of whole blood resuscitation in the civilian population is need for it to be transfused without the need for blood typing or cross matching. Of similar importance is the need for cold storage and recycling of any unused whole blood product, allowing maximal utility of this precious resource. Based upon the belief that early whole blood resuscitation represents the most efficacious hemostatic resuscitation product for the management of hemorrhage, the University of Pittsburgh is currently utilizing cold stored, low titer, platelet replete-leukocyte reduced, group O whole blood (LTLR-WB) for urgent release in the emergency department, without the need for blood typing or cross matching, for patients in hemorrhagic shock. The hypothesis is that the initiation of LTLR-WB resuscitation in the prehospital setting with continuation through the in-hospital acute resuscitation phase of care will significantly reduce the morbidity and mortality attributable to hemorrhagic shock post-injury as compared to standard prehospital and in-hospital resuscitation practice. Thus, a large pragmatic clinical trial is needed to definitively establish the efficacy and safety of whole blood resuscitation initiated in the prehospital setting. Only a high quality clinical trial will provide the essential evidence to justify and provide the impetus for the use of this precious blood banking resource early post-injury. Because of the challenges associated with execution of these types of large trials particularly in the prehospital setting, it is essential to establish feasibility of this approach in a pilot study and provide experience to inform a definitive large, multicenter whole blood trial. The University of Pittsburgh has a track record of prehospital interventional trials post-injury and the clinical research infrastructure to successfully execute the following this trial.

Official Title
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Pragmatic Prehospital Group O Whole Blood Early Resuscitation (PPOWER) Trial: A Prospective, Interventional,Randomized, 3 Year, Pilot Clinical Trial

Conditions
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Hemorrhagic Shock

Intervention / Treatment
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* Biological: Whole blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Injured patients being transport via an air medical service with hypotension (SBP =/< 90mmHg with tachycardia >108 OR SBP=/<70 without the tachycardia requirement) Exclusion Criteria: Age < 18 or > 89 years Isolated fall from standing injury mechanism Brain matter exposed or penetrating brain injury (GSW) CPR > 5 mins with out ROSC Isolated burns without evidence of traumatic injury Isolated Drowning or Hanging No Intravenous or Intraosseous access Known prisoner or known pregnancy Referral Hospital Admission Wearing No PPOWER bracelet Objection to study voiced by subject or family at scene

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LTLR-WB<br>Receiving 2 units of low titer, leucocyte reduced, platelet replete whole blood initiated in the prehospital setting during air medical transport and continued (up to 6 units of whole blood followed by standard component resuscitation) thru the early in-hospital phase of care | Biological: Whole blood<br>* Low titer, group O, leukocyte reduced, platelet replete, cold stored whole blood<br>|
| No Intervention: Standard Care<br>Receiving standard prehospital air medical care and standard of care component (1:1:1) trauma resuscitation thru the early in-hospital phase of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 Day All Cause Mortality | 28 day all cause mortality | 28 days from admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Multiple Organ Failure | multiple organ failure using the Denver post-injury MOF score which is a summed score and when the score is 4 or greater from 4 organ system scores, MOF is designated; 4 organ systems (pulmonary [0-3], renal [0-3], hepatic [0-3], cardiovascular [0-3]) | 28 days from admission | 
| 24 Hour Mortality | 24 hour mortality | 24 hours from admission |