Clinical Trial

. 2014 Sep;45(9):1287-95.

doi: 10.1016/j.injury.2014.06.001. Epub 2014 Jun 10.

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

Sarah Baraniuk¹, Barbara C Tilley², Deborah J del Junco³, Erin E Fox³, Gerald van Belle⁴, Charles E Wade³, Jeanette M Podbielski³, Angela M Beeler³, John R Hess⁵, Eileen M Bulger⁶, Martin A Schreiber⁷, Kenji Inaba⁸, Timothy C Fabian⁹, Jeffrey D Kerby¹⁰, Mitchell Jay Cohen¹¹, Christopher N Miller¹², Sandro Rizoli¹³, Thomas M Scalea¹⁴, Terence O'Keeffe¹⁵, Karen J Brasel¹⁶, Bryan A Cotton³, Peter Muskat¹⁷, John B Holcomb³; PROPPR Study Group

Collaborators, Affiliations

Collaborators

PROPPR Study Group:
John B Holcomb, Charles E Wade, Deborah J del Junco, Erin E Fox, Nena Matijevic, Jeanette Podbielski, Angela M Beeler, Barbara C Tilley, Sarah Baraniuk, Joshua Nixon, Hui Yang, Michael O Gonzalez, Savitri N Appana, Roann Seay, Lisa Baer, Savitri N Appana, Roann Seay, Yao-Wei Willa Wang, Brittany S Hula, Elena Espino, An Nguyen, Nicholas Pawelczyk, Kisha D Arora-Nutall, Rishika Sharma, Jessica C Cardenas, Elaheh Rahbar, Tyrone Burnett Jr, David Clark, Gerald van Belle, Susanne May, Brian Leroux, David Hoyt, Judy Powell, Kellie Sheehan, Alan Hubbard, Adam P Arkin, John R Hess, Jeannie Callum, Bryan A Cotton, Laura Vincent, Timothy Welch, Tiffany Poole, Evan G Pivalizza, Sam D Gumbert, Yu Bai, James J McCarthy, Amy Noland, Rhonda Hobbs, Eileen M Bulger, Patricia Klotz, Lindsay Cattin, Keir J Warner, Angela Wilson, David Boman, Nathan White, Andreas Grabinsky, Jennifer A Daniel-Johnson, Mitchell Jay Cohen, Rachael A Callcut, Mary Nelson, Brittney Redick, Amanda Conroy, Marc P Steurer, Preston C Maxim, Eberhard Fiebig, Joanne Moore, Eireen Mallari, Peter Muskat, Jay A Johannigman, Bryce R H Robinson, Richard D Branson, Dina Gomaa, Christopher Barczak, Suzanne Bennett, Patricia M Carey, Christopher N Miller, Helen Hancock, Carolina Rodriguez, Kenji Inaba, Jay G Zhu, Monica D Wong, Michael Menchine, Kelly Katzberg, Sean O Henderson, Rodney McKeever, Ira A Shulman, Janice M Nelson, Christopher W Tuma, Cheryl Y Matsushita, Thomas M Scalea, Deborah M Stein, Cynthia K Shaffer, Christine Wade, Anthony V Herrera, Seeta Kallam, Sarah E Wade, Cynthia K Shaffer, Samuel M Galvagno Jr, Magali J Fontaine, Janice M Hunt, Rhonda K Cooke, Timothy C Fabian, Jordan A Weinberg, Martin A Croce, Suzanne Wilson, Stephanie Panzer-Baggett, Lynda Waddle-Smith, Sherri Flax, Karen J Brasel, Pamela Walsh, David Milia, Allia Nelson, Olga Kaslow, Tom P Aufderheide, Jerome L Gottschall, Erica Carpenter, Terence O'Keeffe, Laurel L Rokowski, Kurt R Denninghoff, Daniel T Redford, Deborah J Novak, Susan Knoll, Jeffrey D Kerby, Jean-Francois Pittet, Patrick L Bosarge, Carolyn R Williams, Shannon W Stephens, Henry E Wang, Marisa B Marques, Martin A Schreiber, Jennifer M Watters, Samantha J Underwood, Tahnee Groat, Craig Newgard, Matthias Merkel, Richard M Scanlan, Beth Miller, Sandro Rizoli, Homer Tien, Barto Nascimento, Sandy Trpcic, Skeeta Sobrian-Couroux, Marciano Reis, Adic Pérez, Susan E Belo, Connie Colavecchia

Affiliations

¹ Division of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, United States. Electronic address: Mary.Baraniuk@uth.tmc.edu.
² Division of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, United States.
³ 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.
⁴ Department of Environmental and Occupational Health Sciences and Department of Biostatistics, School of Public Health, University of Washington, United States.
⁵ Department of Laboratory Medicine, School of Medicine, University of Washington, United States.
⁶ Division of Trauma and Critical Care, Department of Surgery, School of Medicine, University of Washington, United States.
⁷ Division of Trauma, Critical Care and Acute Care Surgery, School of Medicine, Oregon Health & Science University, United States.
⁸ Division of Trauma and Critical Care, University of Southern California, United States.
⁹ Division of Trauma and Surgical Critical Care, Department of Surgery, Medical School, University of Tennessee Health Science Center, United States.
¹⁰ Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, School of Medicine, University of Alabama at Birmingham, United States.
¹¹ Division of General Surgery, Department of Surgery, School of Medicine, University of California, San Francisco, United States.
¹² Department of Emergency Medicine, College of Medicine, University of Cincinnati, United States.
¹³ Trauma and Acute Care Surgery, St Michael's Hospital, University of Toronto, Canada.
¹⁴ R Adams Cowley Shock Trauma Center, Program in Trauma, University of Maryland School of Medicine, United States.
¹⁵ Division of Trauma, Critical Care and Emergency Surgery, Department of Surgery, University of Arizona, United States.
¹⁶ Division of Trauma and Critical Care, Department of Surgery, Medical College of Wisconsin, United States.
¹⁷ Division of Trauma/Critical Care, Department of Surgery, College of Medicine, University of Cincinnati, United States.

PMID: 24996573
PMCID: PMC4137482
DOI: 10.1016/j.injury.2014.06.001

Clinical Trial

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

Sarah Baraniuk et al. Injury. 2014 Sep.

. 2014 Sep;45(9):1287-95.

doi: 10.1016/j.injury.2014.06.001. Epub 2014 Jun 10.

Authors

Collaborators

PROPPR Study Group:
John B Holcomb, Charles E Wade, Deborah J del Junco, Erin E Fox, Nena Matijevic, Jeanette Podbielski, Angela M Beeler, Barbara C Tilley, Sarah Baraniuk, Joshua Nixon, Hui Yang, Michael O Gonzalez, Savitri N Appana, Roann Seay, Lisa Baer, Savitri N Appana, Roann Seay, Yao-Wei Willa Wang, Brittany S Hula, Elena Espino, An Nguyen, Nicholas Pawelczyk, Kisha D Arora-Nutall, Rishika Sharma, Jessica C Cardenas, Elaheh Rahbar, Tyrone Burnett Jr, David Clark, Gerald van Belle, Susanne May, Brian Leroux, David Hoyt, Judy Powell, Kellie Sheehan, Alan Hubbard, Adam P Arkin, John R Hess, Jeannie Callum, Bryan A Cotton, Laura Vincent, Timothy Welch, Tiffany Poole, Evan G Pivalizza, Sam D Gumbert, Yu Bai, James J McCarthy, Amy Noland, Rhonda Hobbs, Eileen M Bulger, Patricia Klotz, Lindsay Cattin, Keir J Warner, Angela Wilson, David Boman, Nathan White, Andreas Grabinsky, Jennifer A Daniel-Johnson, Mitchell Jay Cohen, Rachael A Callcut, Mary Nelson, Brittney Redick, Amanda Conroy, Marc P Steurer, Preston C Maxim, Eberhard Fiebig, Joanne Moore, Eireen Mallari, Peter Muskat, Jay A Johannigman, Bryce R H Robinson, Richard D Branson, Dina Gomaa, Christopher Barczak, Suzanne Bennett, Patricia M Carey, Christopher N Miller, Helen Hancock, Carolina Rodriguez, Kenji Inaba, Jay G Zhu, Monica D Wong, Michael Menchine, Kelly Katzberg, Sean O Henderson, Rodney McKeever, Ira A Shulman, Janice M Nelson, Christopher W Tuma, Cheryl Y Matsushita, Thomas M Scalea, Deborah M Stein, Cynthia K Shaffer, Christine Wade, Anthony V Herrera, Seeta Kallam, Sarah E Wade, Cynthia K Shaffer, Samuel M Galvagno Jr, Magali J Fontaine, Janice M Hunt, Rhonda K Cooke, Timothy C Fabian, Jordan A Weinberg, Martin A Croce, Suzanne Wilson, Stephanie Panzer-Baggett, Lynda Waddle-Smith, Sherri Flax, Karen J Brasel, Pamela Walsh, David Milia, Allia Nelson, Olga Kaslow, Tom P Aufderheide, Jerome L Gottschall, Erica Carpenter, Terence O'Keeffe, Laurel L Rokowski, Kurt R Denninghoff, Daniel T Redford, Deborah J Novak, Susan Knoll, Jeffrey D Kerby, Jean-Francois Pittet, Patrick L Bosarge, Carolyn R Williams, Shannon W Stephens, Henry E Wang, Marisa B Marques, Martin A Schreiber, Jennifer M Watters, Samantha J Underwood, Tahnee Groat, Craig Newgard, Matthias Merkel, Richard M Scanlan, Beth Miller, Sandro Rizoli, Homer Tien, Barto Nascimento, Sandy Trpcic, Skeeta Sobrian-Couroux, Marciano Reis, Adic Pérez, Susan E Belo, Connie Colavecchia

Affiliations

¹ Division of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, United States. Electronic address: Mary.Baraniuk@uth.tmc.edu.
² Division of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, United States.
³ 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.
⁴ Department of Environmental and Occupational Health Sciences and Department of Biostatistics, School of Public Health, University of Washington, United States.
⁵ Department of Laboratory Medicine, School of Medicine, University of Washington, United States.
⁶ Division of Trauma and Critical Care, Department of Surgery, School of Medicine, University of Washington, United States.
⁷ Division of Trauma, Critical Care and Acute Care Surgery, School of Medicine, Oregon Health & Science University, United States.
⁸ Division of Trauma and Critical Care, University of Southern California, United States.
⁹ Division of Trauma and Surgical Critical Care, Department of Surgery, Medical School, University of Tennessee Health Science Center, United States.
¹⁰ Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, School of Medicine, University of Alabama at Birmingham, United States.
¹¹ Division of General Surgery, Department of Surgery, School of Medicine, University of California, San Francisco, United States.
¹² Department of Emergency Medicine, College of Medicine, University of Cincinnati, United States.
¹³ Trauma and Acute Care Surgery, St Michael's Hospital, University of Toronto, Canada.
¹⁴ R Adams Cowley Shock Trauma Center, Program in Trauma, University of Maryland School of Medicine, United States.
¹⁵ Division of Trauma, Critical Care and Emergency Surgery, Department of Surgery, University of Arizona, United States.
¹⁶ Division of Trauma and Critical Care, Department of Surgery, Medical College of Wisconsin, United States.
¹⁷ Division of Trauma/Critical Care, Department of Surgery, College of Medicine, University of Cincinnati, United States.

PMID: 24996573
PMCID: PMC4137482
DOI: 10.1016/j.injury.2014.06.001

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.

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 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01545232.

Keywords: Clinical trial; Plasma; Platelets; Resuscitation; Transfusion; Trauma.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest Statement:

No conflicts of interest have been declared by any author in regards to this manuscript.

Figures

**Figure 1**
PROPPR Administrative Structure and Participating Sites

**Figure 3**
Recruitment graph. The vertical lines in the above figure indicate 25%, 50%, and 75% of the planned accrual period elapsed, respectively. The red vertical line indicates the end of the Vanguard stage. The red, orange and yellow shaded areas represent NHLBIs level of concern with low enrolling studies.

See this image and copyright information in PMC

References

1. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007;62:307–310. - PubMed
1. Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma. 2006;60:S3–S11. - PubMed
1. Kauvar DS, Wade CE. The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. Crit Care. 2005;9(Suppl 5):S1–S9. - PMC - PubMed
1. Perkins JG, Cap AP, Spinella PC, Blackbourne LH, Grathwohl KW, Repine TB, et al. An evaluation of the impact of apheresis platelets used in the setting of massively transfused trauma patients. J Trauma. 2009;66:S77–S84. discussion S-5. - PubMed
1. Demetriades D, Murray J, Charalambides K, Alo K, Velmahos G, Rhee P, et al. Trauma fatalities: time and location of hospital deaths. J Am Coll Surg. 2004;198:20–26. - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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