Control of Major Bleeding After Trauma Study

Study Overview
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Brief Summary
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Bleeding is the most avoidable cause of death in trauma patients. Up to one-third of severely injured trauma patients are found to be coagulopathic and forty percent of the mortality following severe injury is due to uncontrollable hemorrhage in the setting of coagulopathy. It has been established that early administration of fresh frozen plasma decreases mortality following severe injury, replacing lost coagulation factors, improving the coagulopathy and restoring blood volume. This study will determine if giving plasma to severely injured trauma patients during ambulance transport versus after arrival to the hospital will help reduce hemorrhage, thus decreasing both total blood product administration and mortality.

Detailed Description
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Study Design: Severely injured trauma patients with a systolic blood pressure (SBP) ≤ 70 or SBP ≤ 90 with a heart rate ≥ 108 bpm at the scene will be enrolled and randomized to receive either 2 units of frozen plasma thawed in the field or normal saline (the current standard of care), as the initial resuscitation fluid. After this initial resuscitation fluid, both groups will receive the same standard of care, including packed red blood cells, additional normal saline, or plasma as needed based on laboratory and clinical evidence of coagulopathy. Blood samples and clinical information will be collected throughout the hospital stay up to 28 days after injury.

Official Title
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A Prospective, Randomized Comparison of Fresh Frozen Plasma Versus Standard Crystalloid Intravenous Fluid as Initial Resuscitation Fluid

Conditions
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Trauma, Hemorrhagic Shock

Intervention / Treatment
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* Biological: Type AB plasma
* Drug: Crystalloid fluid (standard of care for resuscitation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>=18 years Acutely injured SBP<70 mmHg or SBP 71-90 mmHg with heart rate (HR)>108 beats per minute. Exclusion Criteria: Visibly or verbally reported pregnant women known prisoners unsalvageable injuries (defined as asystolic or cardiopulmonary resuscitation prior to randomization) known objection to blood products the patient has an opt-out bracelet or, necklace or wallet card a family member present at the scene objects to the patient's enrollment in research.

Ages Eligible for Study
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Minimum Age: 18 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: Plasma<br>If the patient is randomized to experimental arm, 2 units of frozen type AB plasma (FP24) will be thawed in the Plasmatherm Dry Thawing and Warming Device according to the operator manual as approved by the FDA in the ambulance and infusion will commence as soon as the type AB plasma is ready, and will continue during transport to the emergency department (ED). After infusion of 2 units of type AB plasma is completed, subsequent care will proceed per institutional, Advanced Trauma Life Support (ATLS) guided resuscitation with acute packed red blood cells (pRBC) administration determined by the hemodynamic response and additional blood component administration guided by rapid thrombelastography (rTEG) and coagulation panel assessment in conjunction with clinical scenario. | Biological: Type AB plasma<br>* The plasma is thawed and administered to subjects in the experimental (plasma) arm.<br>* Other names: Plasma frozen within 24 hours (FP24, PF24);|
| Active Comparator: Standard<br>If the patient is randomized to the standard arm, the patient will be given intravenous crystalloid fluid (normal saline) as the initial resuscitation fluid with 2 large bore IVs based on the current ATLS guidelines, the standard of care. Subsequent care will proceed per institutional, ATLS guided resuscitation with acute packed red blood cells pRBC administration determined by the hemodynamic response and additional blood component administration guided by rTEG and coagulation panel assessment in conjunction with clinical scenario. | Drug: Crystalloid fluid (standard of care for resuscitation)<br>* Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Died Within 28 Days Post Injury | death within 28 days post injury (death of any cause except for death due to a second, clearly unrelated traumatic injury suffered after discharge) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence | The occurrence of in-hospital death or MOF within the first 28 days postinjury. MOF is defined using the validated Denver MOF score (Denver MOF score>3 of simultaneously obtained scores after 48 hours postinjury). | 28 days | 
| Admission Coagulopathy | Defined as the first international normalized ratio (INR) obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. | within 30 minutes of Emergency Department (ED) arrival | 
| Number of Participants With Admission Severe Coagulopathy | Defined as international normalized ratio (INR) >1.3 obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. | within 30 minutes of Emergency Department (ED) arrival | 
| Admission Clot Strength | Admission clot strength will be measured by thrombelastography G-value upon ED arrival. Clot strength measured in kilodynes per square centimetre (kdyn/cm^2). | within 30 minutes of ED arrival | 
| Admission Acidosis | Admission acidosis measured by lactate upon ED arrival. | within 30 minutes of ED arrival | 
| Number of Participants With Admission Severe Acidosis | Admission severe acidosis measured by lactate>5 upon ED arrival. | within 30 minutes of ED arrival | 
| Admission Acidosis | Admission acidosis will be defined by base deficit (BD) upon ED arrival. | within 30 minutes of ED arrival | 
| Number of Participants With Admission Severe Acidosis | Admission severe acidosis will be defined by base deficit (BD>10) upon ED arrival. | within 30 minutes of ED arrival | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coagulopathy, hemorrhagic shock, plasma, blood product transfusion