Clinical trial NCT01545232: Pragmatic, Randomized Optimal Platelet and Plasma Ratios
Official title: Pragmatic, Randomized Optimal Platelet and Plasma Ratios
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Resuscitation Outcomes Consortium
name: Defence Research and Development Canada
First posted: 2012-03-06
Enrollment: 680
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 24-hour Mortality
timeFrame: First 24 hours after ED admission
measure: 30-day Mortality
timeFrame: First 30 days after ED admission
measure: Coagulation as Indicated by Number of Participants With Reported Venous Thrombolic Events (VTE)
timeFrame: From time of ED admission, for up to 72 hours
Secondary outcomes:
measure: Hospital Free Days
timeFrame: first 30 days after ED admission
measure: Time to Hemostasis
timeFrame: ED admission to hospital discharge or 30 days, whichever comes first
measure: Amount of Randomized Blood Products Given to Hemostasis
timeFrame: 24 hours from randomization
measure: Functional Status at Time of Hospital Discharge
timeFrame: Hospital discharge or 30 days, whichever comes first
measure: Incidence of Primary Surgical Procedure
timeFrame: ED admission to hospital discharge or 30 days, whichever comes first
measure: Incidence of Transfusion Related Serious Adverse Events
timeFrame: ED admission to hospital discharge or 30 days, whichever comes first
measure: Initial Hospital Discharge Status
timeFrame: Hospital discharge or 30 days, whichever comes first
measure: Ventilator Free Days
timeFrame: first 30 days after ED admission
measure: ICU Free Days
timeFrame: first 30 days after ED admission
measure: Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission
timeFrame: 24 hours after ED admission
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center- Memorial Hermann Hospital
state: Texas
city: Seattle
country: United States
facility: University of Washington- Harborview Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Sunnybrook Health Science Center
state: Ontario
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: John Holcomb, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.