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

Sarah Baraniuk, Barbara C Tilley, Deborah J del Junco, Erin E Fox, Gerald van Belle, Charles E Wade, Jeanette M Podbielski, Angela M Beeler, John R Hess, Eileen M Bulger, Martin A Schreiber, Kenji Inaba, Timothy C Fabian, Jeffrey D Kerby, Mitchell Jay Cohen, Christopher N Miller, Sandro Rizoli, Thomas M Scalea, Terence O'Keeffe, Karen J Brasel, Bryan A Cotton, Peter Muskat, John B Holcomb, 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, Sarah Baraniuk, Barbara C Tilley, Deborah J del Junco, Erin E Fox, Gerald van Belle, Charles E Wade, Jeanette M Podbielski, Angela M Beeler, John R Hess, Eileen M Bulger, Martin A Schreiber, Kenji Inaba, Timothy C Fabian, Jeffrey D Kerby, Mitchell Jay Cohen, Christopher N Miller, Sandro Rizoli, Thomas M Scalea, Terence O'Keeffe, Karen J Brasel, Bryan A Cotton, Peter Muskat, John B Holcomb, 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

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.