Pragmatic, Randomized Optimal Platelet and Plasma Ratios

Trauma Clinical Trial

— PROPPR  

Official title:

Pragmatic, Randomized Optimal Platelet and Plasma Ratios

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01545232
• Other study ID #: HSC-GEN-11-0174
• Secondary ID: U01HL077863
• Status: Completed
• Phase: Phase 3
• Start date: August 2012
• Est. completion date: December 2013

Study information

• Verified date: February 2019
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 680
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Trauma

Intervention

Biological:
• 1:1:1 Blood Transfusion Ratio
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.
• 1:1:2 Blood Transfusion Ratio
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.

Locations

Country	Name	City	State
Canada	Sunnybrook Health Science Center	Toronto	Ontario
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Health Science Center- Memorial Hermann Hospital	Houston	Texas
United States	University of Southern California, Los Angeles	Los Angeles	California
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Oregon Health and Science University	Portland	Oregon
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington- Harborview Medical Center	Seattle	Washington
United States	University of Arizona	Tucson	Arizona

Sponsors (5)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	Defence Research and Development Canada, National Heart, Lung, and Blood Institute (NHLBI), Resuscitation Outcomes Consortium, United States Department of Defense

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-hour Mortality		First 24 hours after ED admission
Primary	30-day Mortality		First 30 days after ED admission
Primary	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	Hospital Free Days		first 30 days after ED admission
Secondary	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
Secondary	Amount of Randomized Blood Products Given to Hemostasis		24 hours from randomization
Secondary	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
Secondary	Incidence of Primary Surgical Procedure		ED admission to hospital discharge or 30 days, whichever comes first
Secondary	Incidence of Transfusion Related Serious Adverse Events		ED admission to hospital discharge or 30 days, whichever comes first
Secondary	Initial Hospital Discharge Status		Hospital discharge or 30 days, whichever comes first
Secondary	Ventilator Free Days		first 30 days after ED admission
Secondary	ICU Free Days		first 30 days after ED admission
Secondary	Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission		24 hours after ED admission

External Links

•   ROC web site