Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial: Design, rationale and implementation

Abstract

Background Forty percent of in-hospital deaths among injured patients involve massive truncal hemorrhage. These deaths may be prevented with rapid hemorrhage control and improved resuscitation techniques. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial was designed to determine if there is a difference in mortality between subjects who received different ratios of FDA approved blood products. This report describes the design and implementation of PROPPR. Study Design PROPPR was designed as a randomized, two-group, Phase III trial conducted in subjects with the highest level of trauma activation and predicted to have a massive transfusion. Subjects at 12 North American level 1 trauma centers were randomized into one of two standard transfusion ratio interventions: 1:1:1 or 1:1:2, (plasma, platelets, and red blood cells). Clinical data and serial blood samples were collected under Exception from Informed Consent (EFIC) regulations. Co-primary mortality endpoints of 24 hours and 30 days were evaluated. Results Between August 2012 and December 2013, 680 patients were randomized. The overall median time from admission to randomization was 26 minutes. PROPPR enrolled at higher than expected rates with fewer than expected protocol deviations. Conclusion PROPPR is the largest randomized study to enroll severely bleeding patients. This study showed that rapidly enrolling and successfully providing randomized blood products to severely injured patients in an EFIC study is feasible. PROPPR was able to achieve these goals by utilizing a collaborative structure and developing successful procedures and design elements that can be part of future trauma studies.

How I treat patients with massive hemorrhage

“…53 A much warranted multicenter randomized clinical study Pragmatic, Randomized Optimal Platelets and Plasma Ratios (clinicaltrials.gov identifier #NCT01545232) evaluating 2 different ratios of FFPs:PCs:RBCs (1:1:1 vs 1:1:2) in 680 trauma patients who were predicted to require massive transfusions finished enrollment December 2013, and the results of this study may guide the compositions of future MTP. 54 It should be noted that using fixed ratios may increase the wastage of FFPs and PCs, although recently published data indicate that this problem can be adequately addressed. 55 Conversely, most transfusion data suggest that early balanced transfusion decreases overall use of blood products while improving survival.…”

“…54 Authorship Contribution: P.I.J., S.R.O., R.O., J.S., C.E.W., and J.B.H. wrote and reviewed the manuscript, and reviewed and approved each other's sections.…”

Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial

“…29 This study was conducted with approval from the US Food and Drug Administration and the Department of Defense and in accordance with all local committees for the protection of human subjects under exception from informed consent. 30 All authors had access to and approval to access the primary clinical trial data.…”

“…22,30 Briefly, patients were eligible for enrollment if they were an institutional highest-level trauma activation, were $15 years of age, were received directly from the injury scene, had been transfused with at least 1 unit of blood product within the first hour of arrival or prehospital, and were predicted to receive a massive transfusion. Patients were excluded if they were transferred from another hospital, had a lethal traumatic brain injury, were prisoners, were pregnant, were ,15 years of age, had received .5 minutes of cardiopulmonary resuscitation, had a .20% total bodysurface area burn, had an inhalation injury, or had .3 units of RBCs transfused.…”

Management of traumatic haemorrhage – the US perspective

“…Results of these studies are more mixed, with some showing a benefit associated with early plasma and others showing no effect. The obvious need for better data led to the pragmatic randomised optimal platelet and plasma ratios study, conducted from August 2012 to December 2013 and presently undergoing analysis (www.clinicaltrials.gov, NCT01545232) [14]. A total of 680 haemorrhaging trauma patients were randomly assigned to receive red cells, plasma and platelets, at a ratio of 1:1:1 vs 2:1:1.…”