Pre-Hospital Use of Plasma for Traumatic Hemorrhage

Study Overview
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Brief Summary
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Type A Thawed Plasma (TP) will be compared in polytrauma patients who receive only Normal Saline (NS) (standard of care) before arrival at the hospital. The purpose of this study is to determine if prehospital administration of thawed plasma can reduce mortality of patients who have lost a large amount of blood due to their injuries, compared to those receiving standard of care.

Detailed Description
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INVESTIGATIONAL PLAN This will be an open-label, non-blinded, randomized clinical trial to investigate mortality (30 days) and morbidity of Type A thawed Plasma (TP) versus NS infusion at earliest contact, administered by Emergency Medical Service (EMS) supervisors to subjects who have sustained severe Polytrauma / Major hemorrhage (PTr / MH). The total study is expected to last 2 years with 210 patients enrolled. The two EMS agencies involved in the study will each have one EMS supervisor quick-response vehicle (QRV) equipped with an approved, validated refrigeration unit for TP transport. EMS personnel trained in plasma administration and recognition of reactions may administer up to 2 units of TP to subjects approved for study enrollment. Blood samples for coagulation and lipid testing will be drawn prior to TP administration by EMS personnel,and repeated by hospital personnel at 30 minutes, 8 hours, and 24 hours post-injury. This study is approved for Exception from Informed Consent (EFIC). Once the patient has reached VCUMC and has been entered into the VCUMC health care system, the treating team will advise the Study Coordinator (SC) whether or not a subject is able to consent. As the plasma administration will occur in the field prior to arrival to VCUMC, the SC will make every effort possible to obtain consent from the subject or legally authorized representative (LAR) for continued study participation before the next intervention (8 hour blood specimen collection). The attempts to contact the LAR will be documented in detail. If a subject lacks the ability to provide his/her own consent by the end of day 30, the consent signed by the LAR will be the consent document in force at the subject's completion of the study and no further consent will be sought.

Official Title
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Pre-Hospital Use of Plasma for Traumatic Hemorrhage

Conditions
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Shock, Hemorrhagic

Intervention / Treatment
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* Biological: Plasma
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Blunt or penetrating trauma, Blood Pressure (BP) systolic <70 mmHg or BP 70-90 mmHg with Heart Rate (HR) > 108 Beats Per Minute (BPM), Ongoing hemorrhage with unstable vital signs Exclusion Criteria: Wearing opt-out wrist band, Wearing medical alert jewelry / bracelet, etc. indicating Jehovah Witness or similar with objections to blood transfusions, Refusal to participate (by subject or LAR), Communication barrier at the time of eliciting refusal (non-English speaking or non-Spanish speaking), Not expected to survive transport to Virginia Commonwealth University Medical Center (VCUMC), Documented Do Not Resuscitate (DNR) order found, Cardiac arrest or Cardio-Pulmonary Resuscitation (CPR) prior to randomization Penetrating head trauma, Known / obvious pregnancy, Prisoner, Burns > 20% of body surface

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 |
| --- | --- |
| Active Comparator: Type A Thawed Plasma<br>Eligible subjects with polytrauma (PT) and major hemorrhage (MH) will be randomized to receive 2 units of thawed Type A plasma in the pre-hospital setting administered by EMS first responders. An exception from informed consent under 21CFR 50.24 is required since enrollment will occur (for the majority of subjects) before consent can be obtained. | Biological: Plasma<br>* Type A thawed plasma (up to 2 units) will be administered to polytrauma subjects randomized to plasma arm of study<br>* Other names: Thawed Plasma;|
| Placebo Comparator: Normal saline<br>Eligible subjects with polytrauma (PT) and major hemorrhage (MH) will be randomized to receive normal saline in the pre-hospital setting administered by EMS first responders. Normal saline is standard of care | Drug: Normal saline<br>* Normal saline will be administered to polytrauma subjects randomized to normal saline arm of study<br>* Other names: 0.9% Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | all cause mortality | 30 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coagulation function (thromboelastography, RoTEM, Hemodyne, fibrinogen, D-dimer, PFA-100, platelet count, flow cytometry) | thromboelastography, RoTEM, Hemodyne, fibrinogen, D-dimer, PFA-100, platelet count, flow cytometry | 24 hours | 
| Vital signs (blood pressure, pulse, temperature) | blood pressure, pulse, temperature | 24 hours | 
| Blood product utilization (number of red blood cell units, number of plasma units, number of platelet units cryoprecipitate doses) | number of red blood cell units, number of plasma units, number of platelet units cryoprecipitate doses | 30 days | 
| Lipidomic profiles (arachidonic acid, eicosinoid expression, prostacyclin expression) | arachidonic acid, eicosinoid expression, prostacyclin expression | 24 hours | 
| Blood biochemistry (pH, bicarbonate, lactate) | pH, bicarbonate, lactate | 24 hours | 
| Hematology (Hemoglobin, hematocrit) | Hemoglobin, hematocrit | 24 hours | 
| Hospital outcomes (number of cases of multi-system organ failure (MSOF), renal failure, length of hospital stay, length of ICU stay, number of days on a ventilator, number of surgeries, number of infections) | number of cases of multi-system organ failure (MSOF), renal failure, length of hospital stay, length of ICU stay, number of days on a ventilator, number of surgeries, number of infections | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, Hemorrhage, Plasma, Shock, Polytrauma