Pragmatic, Randomized Optimal Platelet and Plasma Ratios

NCT01545232 | Completed Phase 3 Results DMC

• 2 other identifiers: HSC-GEN-11-0174U01HL077863
• Study Type: interventional
• Target: 680
• Locations: 2 countries
• Sites: 12

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• Hospital Free Days

  first 30 days after ED admission

• Time to Hemostasis

  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

  Hospital discharge or 30 days, whichever comes first

• Incidence of Primary Surgical Procedure

  ED admission to hospital discharge or 30 days, whichever comes first

Study Arms (2)

1:1:1 Blood Transfusion Ratio

ACTIVE COMPARATOR

Biological: 1:1:1 Blood Transfusion Ratio

1:1:2 Blood Transfusion Ratio

ACTIVE COMPARATOR

Biological: 1:1:2 Blood Transfusion Ratio

Interventions

1:1:1 Blood Transfusion Ratio 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.

1:1:1 Blood Transfusion Ratio

1:1:2 Blood Transfusion Ratio 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.

1:1:2 Blood Transfusion Ratio

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (12)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Arizona

Tucson, Arizona, 85721, United States

Location

University of Southern California, Los Angeles

Los Angeles, California, 90033, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45221, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38103, United States

Location

University of Texas Health Science Center- Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

University of Washington- Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Sunnybrook Health Science Center

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (11)

• 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.

  PMID: 37058726 DERIVED

• 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.

  PMID: 33797501 DERIVED

• 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.

  PMID: 31050809 DERIVED

• 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.

  PMID: 30447946 DERIVED

• 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.

  PMID: 30030268 DERIVED

• 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.

  PMID: 29766088 DERIVED

• 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.

  PMID: 28930959 DERIVED

• 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.

  PMID: 28731937 DERIVED

• 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.

  PMID: 25647203 DERIVED

• 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.

  PMID: 24996573 DERIVED

• 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.

  PMID: 24335442 DERIVED

MeSH Terms

Conditions

Wounds and Injuries; Hemostatic Disorders; Shock, Hemorrhagic; Shock; Pathologic Processes; Hemorrhage; Thrombosis; Transfusion-Related Acute Lung Injury; Inflammation

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Acute Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Transfusion Reaction; Immune System Diseases

Results Point of Contact

• Title: John Holcomb, M.D.
• Organization: University of Texas Health Science Center - Houston

John.Holcomb@uth.tmc.edu

713-500-5493

Study Officials

• John Holcomb, MD

  The University of Texas Health Science Center, Houston

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Director

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 6, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 8, 2019
• Results First Posted: June 3, 2015

Record last verified: 2019-02

Locations

CA (1); US (11)