Pragmatic, Randomized Optimal Platelet and Plasma Ratios

NCT ID: NCT01545232

Last Updated: 2019-02-08

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

680 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2013-12-31

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.

Conditions

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Trauma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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1:1:1 Blood Transfusion Ratio

Group Type ACTIVE_COMPARATOR

1:1:1 Blood Transfusion Ratio

Intervention Type BIOLOGICAL

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 Type ACTIVE_COMPARATOR

1:1:2 Blood Transfusion Ratio

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type BIOLOGICAL

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.

Intervention Type BIOLOGICAL

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.
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Resuscitation Outcomes Consortium

NETWORK

Sponsor Role collaborator

Defence Research and Development Canada

INDUSTRY

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

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John Holcomb

Study Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John Holcomb, MD

Role: STUDY_DIRECTOR

The University of Texas Health Science Center, Houston

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

University of Southern California, Los Angeles

Los Angeles, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

University of Tennessee Health Science Center

Memphis, Tennessee, United States

Site Status

University of Texas Health Science Center- Memorial Hermann Hospital

Houston, Texas, United States

Site Status

University of Washington- Harborview Medical Center

Seattle, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Sunnybrook Health Science Center

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Levy DT, Livingston CE, Saroukhani S, Fox EE, Wade CE, Holcomb JB, Gumbert SD, Galvagno SM Jr, Kaslow OY, Pittet JF, Pivalizza EG. Association of Opioid Administration During General Anesthesia and Survival for Severely Injured Trauma Patients: A Preplanned Secondary Analysis of the PROPPR Study. Anesth Analg. 2023 May 1;136(5):905-912. doi: 10.1213/ANE.0000000000006456. Epub 2023 Apr 14.

Reference Type DERIVED
PMID: 37058726 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33797501 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31050809 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30447946 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30030268 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29766088 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28930959 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28731937 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25647203 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24996573 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24335442 (View on PubMed)

Other Identifiers

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U01HL077863

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-GEN-11-0174

Identifier Type: -

Identifier Source: org_study_id

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