title: 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 haemorrhage. These deaths may be prevented with rapid haemorrhage 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.
  
  
  METHODS
  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 centres 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 24h 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 26min. PROPPR enrolled at higher than expected rates with fewer than expected protocol deviations.
  
  
  CONCLUSIONS
  PROPPR is the largest randomized study to enrol 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.
authors.affiliation: Division of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, United States. Electronic address: Mary.Baraniuk@uth.tmc.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baraniuk
authors.affiliation: Division of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, United States.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Tilley
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: del Junco
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Fox
authors.affiliation: Department of Environmental and Occupational Health Sciences and Department of Biostatistics, School of Public Health, University of Washington, United States.
authors.forename: Gerald
authors.initials: G
authors.lastname: van Belle
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wade
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Podbielski
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Beeler
authors.affiliation: Department of Laboratory Medicine, School of Medicine, University of Washington, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Hess
authors.affiliation: Division of Trauma and Critical Care, Department of Surgery, School of Medicine, University of Washington, United States.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
authors.affiliation: Division of Trauma, Critical Care and Acute Care Surgery, School of Medicine, Oregon Health & Science University, United States.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
authors.affiliation: Division of Trauma and Critical Care, University of Southern California, United States.
authors.forename: Kenji
authors.initials: K
authors.lastname: Inaba
authors.affiliation: Division of Trauma and Surgical Critical Care, Department of Surgery, Medical School, University of Tennessee Health Science Center, United States.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Fabian
authors.affiliation: Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, School of Medicine, University of Alabama at Birmingham, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kerby
authors.affiliation: Division of General Surgery, Department of Surgery, School of Medicine, University of California, San Francisco, United States.
authors.forename: Mitchell Jay
authors.initials: MJ
authors.lastname: Cohen
authors.affiliation: Department of Emergency Medicine, College of Medicine, University of Cincinnati, United States.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Miller
authors.affiliation: Trauma and Acute Care Surgery, St Michael's Hospital, University of Toronto, Canada.
authors.forename: Sandro
authors.initials: S
authors.lastname: Rizoli
authors.affiliation: R Adams Cowley Shock Trauma Center, Program in Trauma, University of Maryland School of Medicine, United States.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Scalea
authors.affiliation: Division of Trauma, Critical Care and Emergency Surgery, Department of Surgery, University of Arizona, United States.
authors.forename: Terence
authors.initials: T
authors.lastname: O'Keeffe
authors.affiliation: Division of Trauma and Critical Care, Department of Surgery, Medical College of Wisconsin, United States.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Brasel
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Cotton
authors.affiliation: Division of Trauma/Critical Care, Department of Surgery, College of Medicine, University of Cincinnati, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Muskat
authors.affiliation: Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, United States.
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets; D001803:Blood Transfusion / Q000379:methods* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D058734:Exsanguination / Q000401:mortality / Q000628:therapy*; D005260:Female; D006470:Hemorrhage / Q000401:mortality*; D006487:Hemostasis; D017052:Hospital Mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D010949:Plasma; D012151:Resuscitation / Q000379:methods* / Q000401:mortality; D015996:Survival Rate; D014193:Trauma Centers / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000401:mortality / Q000628:therapy*
keywords: Clinical trial; Plasma; Platelets; Resuscitation; Transfusion; Trauma