Control of Major Bleeding After Trauma Study

Phase 2

Terminated

Conditions: Trauma
Hemorrhagic Shock

Interventions: Biological: Type AB plasma
Drug: Crystalloid fluid (standard of care for resuscitation)

Registration Number: NCT01838863

Lead Sponsor: Denver Health and Hospital Authority

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 144

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plasma	Type AB plasma	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.
Standard	Crystalloid fluid (standard of care for resuscitation)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Admission Severe Coagulopathy	within 30 minutes of Emergency Department (ED) arrival	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.
Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence	28 days	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).
Admission Coagulopathy	within 30 minutes of Emergency Department (ED) arrival	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.
Admission Clot Strength	within 30 minutes of ED arrival	Admission clot strength will be measured by thrombelastography G-value upon ED arrival. Clot strength measured in kilodynes per square centimetre (kdyn/cm\^2).
Admission Acidosis	within 30 minutes of ED arrival	Admission acidosis will be defined by base deficit (BD) upon ED arrival.
Number of Participants With Admission Severe Acidosis	within 30 minutes of ED arrival	Admission severe acidosis will be defined by base deficit (BD\>10) upon ED arrival.