Pragmatic, Randomized Optimal Platelet and Plasma Ratios

Study Overview
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Brief Summary
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Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR)is a Phase III trial designed to evaluate the difference in 24-hour and 30-day mortality among subjects predicted to receive massive transfusion ([MT] (defined as receiving 10 units or more red blood cells (RBCs) within the first 24 hours). The goal of PROPPR is to improve the basis on which clinicians make decisions about transfusion protocols for massively bleeding patients. PROPPR is a Resuscitation Outcomes Consortium (ROC) Protocol. ROC is funded by the National Heart, Lung, and Blood Institute (NHLBI), the United States' Department of Defense (DoD) and the Defence Research and Development Canada. PROPPR will be conducted as a Phase III trial at Level I Adult Trauma Centers in North America.

Detailed Description
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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.

Official Title
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Pragmatic, Randomized Optimal Platelet and Plasma Ratios

Conditions
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Trauma

Intervention / Treatment
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* Biological: 1:1:1 Blood Transfusion Ratio
* Biological: 1:1:2 Blood Transfusion Ratio


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 15 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 |
| --- | --- |
| Active Comparator: 1:1:1 Blood Transfusion Ratio<br> | Biological: 1:1:1 Blood Transfusion Ratio<br>* Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.<br>|
| Active Comparator: 1:1:2 Blood Transfusion Ratio<br> | Biological: 1:1:2 Blood Transfusion Ratio<br>* Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour Mortality |  | First 24 hours after ED admission | 
| 30-day Mortality |  | First 30 days after ED admission | 
| Coagulation as Indicated by Number of Participants With Reported Venous Thrombolic Events (VTE) | Blood samples were collected at time of ED admission and over time to determine the incidence of reported venous thrombolic events (VTE). | From time of ED admission, for up to 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Free Days |  | first 30 days after ED admission | 
| Time to Hemostasis | Time to hemostasis refers to the time that the subject achieved hemorrhage control (anatomic hemostasis and resuscitation complete)following emergency department (ED) arrival. | ED admission to hospital discharge or 30 days, whichever comes first | 
| Amount of Randomized Blood Products Given to Hemostasis |  | 24 hours from randomization | 
| Functional Status at Time of Hospital Discharge | The Glasgow Outcome Extended Score (GOSE) is a tool used to measure recovery following brain injury and assists with prediction of long-term rehabilitation. The 8 scoring categories are death, vegetative state, lower severe disability, upper severe disability, lower moderate disability, upper moderate disability, lower good recovery and upper good recovery. A higher GOSE score correlates with better outcome. | Hospital discharge or 30 days, whichever comes first | 
| Incidence of Primary Surgical Procedure |  | ED admission to hospital discharge or 30 days, whichever comes first | 
| Incidence of Transfusion Related Serious Adverse Events |  | ED admission to hospital discharge or 30 days, whichever comes first | 
| Initial Hospital Discharge Status |  | Hospital discharge or 30 days, whichever comes first | 
| Ventilator Free Days |  | first 30 days after ED admission | 
| ICU Free Days |  | first 30 days after ED admission | 
| Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission |  | 24 hours after ED admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coagulation, Transfusion-related acute lung injury (TRALI), Inflammation, Massive Transfusion, Trauma, Coagulopathy, Trauma Induced Coagulopathy, Plasma, Platelets, Red Blood Cells, Mortality, Wounds and Injuries, Shock, Hemorrhagic, Shock, Pathologic Processes, Hemorrhage, Hemostatics