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Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR)

Primary Purpose

Trauma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
1:1:1 Blood Transfusion Ratio
1:1:2 Blood Transfusion Ratio
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Trauma focused on measuring Massive Transfusion, Trauma, Coagulopathy, Trauma Induced Coagulopathy, Plasma, Platelets, Red Blood Cells, Mortality, Wounds and Injuries, Shock, Hemorrhagic, Shock, Pathologic Processes, Hemorrhage, Hemostatics, Coagulation, Transfusion-related acute lung injury (TRALI), Inflammation

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama
  • University of Arizona
  • University of Southern California, Los Angeles
  • University of California, San Francisco
  • University of Maryland School of Medicine
  • University of Cincinnati
  • Oregon Health and Science University
  • University of Tennessee Health Science Center
  • University of Texas Health Science Center- Memorial Hermann Hospital
  • University of Washington- Harborview Medical Center
  • Medical College of Wisconsin
  • Sunnybrook Health Science Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1:1:1 Blood Transfusion Ratio

1:1:2 Blood Transfusion Ratio

Arm Description

Outcomes

Primary Outcome Measures

24-hour Mortality
30-day Mortality
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).

Secondary Outcome Measures

Hospital Free Days
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.
Amount of Randomized Blood Products Given to Hemostasis
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.
Incidence of Primary Surgical Procedure
Incidence of Transfusion Related Serious Adverse Events
Initial Hospital Discharge Status
Ventilator Free Days
ICU Free Days
Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission

Full Information

First Posted
February 29, 2012
Last Updated
February 6, 2019
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
United States Department of Defense, National Heart, Lung, and Blood Institute (NHLBI), Resuscitation Outcomes Consortium, Defence Research and Development Canada
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1. Study Identification

Unique Protocol Identification Number
NCT01545232
Brief Title
Pragmatic, Randomized Optimal Platelet and Plasma Ratios
Acronym
PROPPR
Official Title
Pragmatic, Randomized Optimal Platelet and Plasma Ratios
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
United States Department of Defense, National Heart, Lung, and Blood Institute (NHLBI), Resuscitation Outcomes Consortium, Defence Research and Development Canada

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trauma
Keywords
Massive Transfusion, Trauma, Coagulopathy, Trauma Induced Coagulopathy, Plasma, Platelets, Red Blood Cells, Mortality, Wounds and Injuries, Shock, Hemorrhagic, Shock, Pathologic Processes, Hemorrhage, Hemostatics, Coagulation, Transfusion-related acute lung injury (TRALI), Inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
680 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1:1:1 Blood Transfusion Ratio
Arm Type
Active Comparator
Arm Title
1:1:2 Blood Transfusion Ratio
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
1:1:1 Blood Transfusion Ratio
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
1:1:2 Blood Transfusion Ratio
Intervention Description
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.
Primary Outcome Measure Information:
Title
24-hour Mortality
Time Frame
First 24 hours after ED admission
Title
30-day Mortality
Time Frame
First 30 days after ED admission
Title
Coagulation as Indicated by Number of Participants With Reported Venous Thrombolic Events (VTE)
Description
Blood samples were collected at time of ED admission and over time to determine the incidence of reported venous thrombolic events (VTE).
Time Frame
From time of ED admission, for up to 72 hours
Secondary Outcome Measure Information:
Title
Hospital Free Days
Time Frame
first 30 days after ED admission
Title
Time to Hemostasis
Description
Time to hemostasis refers to the time that the subject achieved hemorrhage control (anatomic hemostasis and resuscitation complete)following emergency department (ED) arrival.
Time Frame
ED admission to hospital discharge or 30 days, whichever comes first
Title
Amount of Randomized Blood Products Given to Hemostasis
Time Frame
24 hours from randomization
Title
Functional Status at Time of Hospital Discharge
Description
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.
Time Frame
Hospital discharge or 30 days, whichever comes first
Title
Incidence of Primary Surgical Procedure
Time Frame
ED admission to hospital discharge or 30 days, whichever comes first
Title
Incidence of Transfusion Related Serious Adverse Events
Time Frame
ED admission to hospital discharge or 30 days, whichever comes first
Title
Initial Hospital Discharge Status
Time Frame
Hospital discharge or 30 days, whichever comes first
Title
Ventilator Free Days
Time Frame
first 30 days after ED admission
Title
ICU Free Days
Time Frame
first 30 days after ED admission
Title
Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission
Time Frame
24 hours after ED admission

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Holcomb, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85721
Country
United States
Facility Name
University of Southern California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Maryland School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45221
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Tennessee Health Science Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
University of Texas Health Science Center- Memorial Hermann Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Washington- Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Sunnybrook Health Science Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
33797501
Citation
McCully BH, Wade CE, Fox EE, Inaba K, Cohen MJ, Holcomb JB, Schreiber MA; PROPPR study group. Temporal profile of the pro- and anti-inflammatory responses to severe hemorrhage in patients with venous thromboembolism: Findings from the PROPPR trial. J Trauma Acute Care Surg. 2021 May 1;90(5):845-852. doi: 10.1097/TA.0000000000003088.
Results Reference
derived
PubMed Identifier
31050809
Citation
DeSantis SM, Brown DW, Jones AR, Yamal JM, Pittet JF, Patel RP, Wade CE, Holcomb JB, Wang H; PROPPR Study Group. Characterizing red blood cell age exposure in massive transfusion therapy: the scalar age of blood index (SBI). Transfusion. 2019 Aug;59(8):2699-2708. doi: 10.1111/trf.15334. Epub 2019 May 3.
Results Reference
derived
PubMed Identifier
30447946
Citation
Jones AR, Patel RP, Marques MB, Donnelly JP, Griffin RL, Pittet JF, Kerby JD, Stephens SW, DeSantis SM, Hess JR, Wang HE; PROPPR Study Group. Older Blood Is Associated With Increased Mortality and Adverse Events in Massively Transfused Trauma Patients: Secondary Analysis of the PROPPR Trial. Ann Emerg Med. 2019 Jun;73(6):650-661. doi: 10.1016/j.annemergmed.2018.09.033. Epub 2018 Nov 15.
Results Reference
derived
PubMed Identifier
30030268
Citation
Cardenas JC, Zhang X, Fox EE, Cotton BA, Hess JR, Schreiber MA, Wade CE, Holcomb JB; PROPPR Study Group. Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial. Blood Adv. 2018 Jul 24;2(14):1696-1704. doi: 10.1182/bloodadvances.2018017699.
Results Reference
derived
PubMed Identifier
29766088
Citation
Henry B, Perez A, Trpcic S, Rizoli S, Nascimento B. Protecting study participants in emergency research: is community consultation before trial commencement enough? Trauma Surg Acute Care Open. 2017 Jul 12;2(1):e000084. doi: 10.1136/tsaco-2017-000084. eCollection 2017.
Results Reference
derived
PubMed Identifier
28930959
Citation
Galvagno SM Jr, Fox EE, Appana SN, Baraniuk S, Bosarge PL, Bulger EM, Callcut RA, Cotton BA, Goodman M, Inaba K, O'Keeffe T, Schreiber MA, Wade CE, Scalea TM, Holcomb JB, Stein DM; PROPPR Study Group. Outcomes after concomitant traumatic brain injury and hemorrhagic shock: A secondary analysis from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios trial. J Trauma Acute Care Surg. 2017 Oct;83(4):668-674. doi: 10.1097/TA.0000000000001584. Epub 2017 Jun 6.
Results Reference
derived
PubMed Identifier
28731937
Citation
Naumann DN, Vincent LE, Pearson N, Beaven A, Smith IM, Smith K, Toman E, Dorrance HR, Porter K, Wade CE, Cotton BA, Holcomb JB, Midwinter MJ. An adapted Clavien-Dindo scoring system in trauma as a clinically meaningful nonmortality endpoint. J Trauma Acute Care Surg. 2017 Aug;83(2):241-248. doi: 10.1097/TA.0000000000001517.
Results Reference
derived
PubMed Identifier
25647203
Citation
Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, del Junco DJ, Brasel KJ, Bulger EM, Callcut RA, Cohen MJ, Cotton BA, Fabian TC, Inaba K, Kerby JD, Muskat P, O'Keeffe T, Rizoli S, Robinson BR, Scalea TM, Schreiber MA, Stein DM, Weinberg JA, Callum JL, Hess JR, Matijevic N, Miller CN, Pittet JF, Hoyt DB, Pearson GD, Leroux B, van Belle G; PROPPR Study Group. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015 Feb 3;313(5):471-82. doi: 10.1001/jama.2015.12.
Results Reference
derived
PubMed Identifier
24996573
Citation
Baraniuk S, Tilley BC, del Junco DJ, Fox EE, van Belle G, Wade CE, Podbielski JM, Beeler AM, Hess JR, Bulger EM, Schreiber MA, Inaba K, Fabian TC, Kerby JD, Cohen MJ, Miller CN, Rizoli S, Scalea TM, O'Keeffe T, Brasel KJ, Cotton BA, Muskat P, Holcomb JB; PROPPR Study Group. Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial: design, rationale and implementation. Injury. 2014 Sep;45(9):1287-95. doi: 10.1016/j.injury.2014.06.001. Epub 2014 Jun 10.
Results Reference
derived
PubMed Identifier
24335442
Citation
Lissauer ME, Galvagno SM Jr, Rock P, Narayan M, Shah P, Spencer H, Hong C, Diaz JJ. Increased ICU resource needs for an academic emergency general surgery service*. Crit Care Med. 2014 Apr;42(4):910-7. doi: 10.1097/CCM.0000000000000099.
Results Reference
derived

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Pragmatic, Randomized Optimal Platelet and Plasma Ratios

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