Pragmatic, Randomized Optimal Platelet and Plasma Ratios

Background: Multiple observational studies have reported that blood product component ratios
(i.e., plasma:platelets:RBCs) that approach the 1:1:1 ratio, found in fresh whole blood, are
associated with significant decreases in truncal hemorrhagic death and in overall 24-hour and
30-day mortality among injured patients. The rationale for the 1:1:1 ratio is that the closer
a transfusion regimen approximates whole blood, the faster hemostasis will be achieved with
minimum risk of coagulopathy. The current DoD guideline specifies the use of 1:1:1, and this
practice is followed on almost all combat casualties. In other observational studies, leading
centers have reported good outcomes across a range of different blood product ratios. For
example, a 1:2 plasma:RBC ratio is used with little guidance regarding platelets. The
proposed randomized trial is intended to resolve debate and uncertainty regarding optimum
blood product ratios.

Study Design: Randomized, two-group, controlled Phase III trial with a Vanguard stage. Equal
random allocation to treatment using stratified, permuted blocks with randomly chosen block
sizes and stratification by site.

Objective: To conduct a Phase III multi-site, randomized trial in subjects predicted to have
a massive transfusion, comparing the efficacy and safety of 1:1:1 transfusion ratios of
plasma and platelets to red blood cells (the closest approximation to reconstituted whole
blood) with the 1:1:2 ratio. The co-primary outcomes will be 24-hour and 30-day mortality.
The PROPPR Trial will be conducted with exception from informed consent (EFIC). Additionally,
laboratory data from the trial will add to the understanding of trauma induced coagulopathy
(TIC) and inflammation.

Inclusion Criteria:

- Subjects who require the highest trauma team activation at each participating center,

- Estimated age of 15 years or older or greater than/equal to weight of 50 kg if age
unknown,

- Received directly from the injury scene,

- Initiated transfusion of at least one unit of blood component within the first hour of
arrival or during prehospital transport, and

- Predicted to receive a MT by exceeding the threshold score of either the Assessment of
Blood Consumption (ABC) score or the attending trauma physician's judgment criteria

Exclusion Criteria:

- Received care (as defined as receiving a life saving intervention) from an outside
hospital or healthcare facility (Procedures and care given at an outside health
facility cannot be documented or controlled resulting in a high variability of
standards of care and clinical outcomes.)

- Moribund patient with devastating injuries and expected to die within one hour of
Emergency Department (ED) admission

- Prisoners, defined as those who have been directly admitted from a correctional
facility

- Patients requiring an emergency thoracotomy

- Children under the age of 15 years or under 50 kg body weight if age unknown

- Known pregnancy in the ED

- Greater than 20% total body surface area (TBSA) burns

- Suspected inhalation injury

- Received greater than five consecutive minutes of cardiopulmonary resuscitation (CPR
with chest compressions) in the pre-arrival or ED setting

- Known Do Not Resuscitate (DNR) prior to randomization

- Enrolled in a concurrent, ongoing interventional, randomized clinical trial

- Patients who have activated the "opt-out" process or patients/legally authorized
representatives that refuse blood products on arrival to ED.