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Pragmatic, Randomized Optimal Platelet and Plasma Ratios

Phase 3
Completed
Conditions
Trauma
Registration Number
NCT01545232
Lead Sponsor
The University of Texas Health Science Center, Houston
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
680
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
24-hour MortalityFirst 24 hours after ED admission
30-day MortalityFirst 30 days after ED admission
Coagulation as Indicated by Number of Participants With Reported Venous Thrombolic Events (VTE)From time of ED admission, for up to 72 hours

Blood samples were collected at time of ED admission and over time to determine the incidence of reported venous thrombolic events (VTE).

Secondary Outcome Measures
NameTimeMethod
Incidence of Primary Surgical ProcedureED admission to hospital discharge or 30 days, whichever comes first
Incidence of Transfusion Related Serious Adverse EventsED admission to hospital discharge or 30 days, whichever comes first
ICU Free Daysfirst 30 days after ED admission
Hospital Free Daysfirst 30 days after ED admission
Time to HemostasisED admission to hospital discharge or 30 days, whichever comes first

Time to hemostasis refers to the time that the subject achieved hemorrhage control (anatomic hemostasis and resuscitation complete)following emergency department (ED) arrival.

Amount of Randomized Blood Products Given to Hemostasis24 hours from randomization
Initial Hospital Discharge StatusHospital discharge or 30 days, whichever comes first
Ventilator Free Daysfirst 30 days after ED admission
Functional Status at Time of Hospital DischargeHospital discharge or 30 days, whichever comes first

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.

Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission24 hours after ED admission

Trial Locations

Locations (12)

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

University of Texas Health Science Center- Memorial Hermann Hospital

🇺🇸

Houston, Texas, United States

University of Alabama

🇺🇸

Birmingham, Alabama, United States

University of Southern California, Los Angeles

🇺🇸

Los Angeles, California, United States

University of California, San Francisco

🇺🇸

San Francisco, California, United States

University of Tennessee Health Science Center

🇺🇸

Memphis, Tennessee, United States

University of Washington- Harborview Medical Center

🇺🇸

Seattle, Washington, United States

Sunnybrook Health Science Center

🇨🇦

Toronto, Ontario, Canada

University of Arizona

🇺🇸

Tucson, Arizona, United States

University of Maryland School of Medicine

🇺🇸

Baltimore, Maryland, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

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