Design of the Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) Trial: Addressing the Knowledge Gaps

References

• 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:S3–11.
   PubMed Web of Science ®Google Scholar
• MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55:39–44.
   PubMed Web of Science ®Google Scholar
• Rahbar E, Fox EE, del Junco DJ, Harvin JA, Holcomb JB, Wade CE, Schreiber MA, Rahbar MH, Bulger EM, Phelan HA, Brasel KJ, Alarcon LH, Myers JG, Cohen MJ, Muskat P, Cotton BA. Early resuscitation intensity as a surrogate for bleeding severity and early mortality in the PROMMTT study. J Trauma Acute Care Surg. 2013;75:S16–S23.
   PubMed Web of Science ®Google Scholar
• Shackford SR, Mackersie RC, Holbrook TL, Davis JW, Hollingsworth-Fridlund P, Hoyt DB, Wolf PL. The epidemiology of traumatic death: a population-based analysis. Arch Surg. 1993;128:571–5.
   PubMed Web of Science ®Google Scholar
• Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54:1127–30.
   PubMed Web of Science ®Google Scholar
• Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, Levrat A, Guillaume C, Marcotte G, Vulliez A, Hautin E, David JS, Negrier C, Allaouchiche B. Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury. 2012;43:26–32.
   PubMed Web of Science ®Google Scholar
• Trentzsch H, Huber-Wagner S, Hildebrand F, Kanz KG, Faist E, Piltz S, Lefering R, TraumaRegistry DGU. Hypothermia for prediction of death in severely injured blunt trauma patients. Shock. 2012;37:131–9.
   PubMed Web of Science ®Google Scholar
• Brown JB, Cohen MJ, Minei JP, Maier RV, West MA, Billiar TR, Peitzman AB, Moore EE, Cuschieri J, Sperry JL, Inflammation, the Host Response to Injury Investigators. Characterization of acute coagulopathy and sexual dimorphism after injury: females and coagulopathy just do not mix. J Trauma Acute Care Surg. 2012;73:1395–400.
   PubMed Web of Science ®Google Scholar
• Niles SE, McLaughlin DF, Perkins JG, Wade CE, Li Y, Spinella PC, Holcomb JB. Increased mortality associated with the early coagulopathy of trauma in combat casualties. J Trauma. 2008;64:1459–63; discussion 1463–5.
   PubMedGoogle Scholar
• Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg. 2007;245:812–8.
   PubMed Web of Science ®Google Scholar
• Burk AM, Martin M, Flierl MA, Rittirsch D, Helm M, Lampl L, Bruckner U, Stahl GL, Blom AM, Perl M, Gebhard F, Huber-Lang M. Early complementopathy after multiple injuries in humans. Shock. 2012;37:348–54.
   PubMed Web of Science ®Google Scholar
• Cohen MJ, West M. Acute traumatic coagulopathy: from endogenous acute coagulopathy to systemic acquired coagulopathy and back. J Trauma. 2011;70:S47–49.
   PubMed Web of Science ®Google Scholar
• Ganter MT, Brohi K, Cohen MJ, Shaffer LA, Walsh MC, Stahl GL, Pittet JF. Role of the alternative pathway in the early complement activation following major trauma. Shock. 2007;28:29–34.
   PubMed Web of Science ®Google Scholar
• Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, Kluger Y, Mackway-Jones K, Parr MJ, Rizoli SB, Yukioka T, Hoyt DB, Bouillon B. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008;65:748–54.
   PubMed Web of Science ®Google Scholar
• Maegele M, Schöchl H, Cohen MJ. An up-date on the coagulopathy of trauma. Shock. 2014;41(Suppl 1):21–5.
   PubMed Web of Science ®Google Scholar
• Kashuk JL, Moore EE, Sawyer M, Wohlauer M, Pezold M, Barnett C, Biffl WL, Burlew CC, Johnson JL, Sauaia A. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg. 2010;252:434–42; discussion 443–4.
   PubMed Web of Science ®Google Scholar
• Cotton BA, Harvin JA, Kostousouv V, Minei KM, Radwan ZA, Schochl H, Wade CE, Holcomb JB, Matijevic N. Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. J Trauma Acute Care Surg. 2012;73:365–70.
   PubMed Web of Science ®Google Scholar
• Ives C, Inaba K, Branco BC, Okoye O, Schochl H, Talving P, Lam L, Shulman I, Nelson J, Demetriades D. Hyperfibrinolysis elicited via thromboelastography predicts mortality in trauma. J Am Coll Surg. 2012;215:496–502.
   PubMed Web of Science ®Google Scholar
• Maegele M, Spinella PC, Schochl H. The acute coagulopathy of trauma: mechanisms and tools for risk stratification. Shock. 2012;38:450–8.
   PubMed Web of Science ®Google Scholar
• Kutcher ME, Cripps MW, McCreery RC, Crane IM, Greenberg MD, Cachola LM, Redick BJ, Nelson MF, Cohen MJ. Criteria for empiric treatment of hyperfibrinolysis after trauma. J Trauma Acute Care Surg. 2012;73:87–93.
   PubMed Web of Science ®Google Scholar
• Chapman MP, Moore EE, Ramos CR, Ghasabyan A, Harr JN, Chin TL, Stringham JR, Sauaia A, Silliman CC, Banerjee A. Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy. J Trauma Acute Care Surg. 2013;75:961–7; discussion 967.
   PubMed Web of Science ®Google Scholar
• Raza I, Davenport R, Rourke C, Platton S, Manson J, Spoors C, Khan S, De'Ath HD, Allard S, Hart DP, Pasi KJ, Hunt BJ, Stanworth S, MacCallum PK, Brohi K. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost. 2013;11:307–14.
   PubMed Web of Science ®Google Scholar
• Medcalf RL. Fibrinolysis, inflammation, and regulation of the plasminogen activating system. J Thromb Haemost. 2007;5 (Suppl 1):132–42.
   PubMed Web of Science ®Google Scholar
• Syrovets T, Lunov O, Simmet T. Plasmin as a proinflammatory cell activator. J Leukoc Biol. 2012;92:509–19.
   PubMed Web of Science ®Google Scholar
• Levy JH. Antifibrinolytic therapy: new data and new concepts. Lancet. 2010;376:3–4.
   PubMed Web of Science ®Google Scholar
• Chang M, Kistler EB, Schmid-Schonbein GW. Disruption of the mucosal barrier during gut ischemia allows entry of digestive enzymes into the intestinal wall. Shock. 2012;37:297–305.
   PubMed Web of Science ®Google Scholar
• Jimenez JJ, Iribarren JL, Lorente L, Rodriguez JM, Hernandez D, Nassar I, Perez R, Brouard M, Milena A, Martinez R, Mora ML. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Crit Care. 2007;11:R117.
   PubMed Web of Science ®Google Scholar
• Dalle Lucca JJ, Li Y, Simovic M, Pusateri AE, Falabella M, Dubick MA, Tsokos GC. Effects of C1 inhibitor on tissue damage in a porcine model of controlled hemorrhage. Shock. 2012;38:82–91.
   PubMed Web of Science ®Google Scholar
• Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23–32.
   PubMed Web of Science ®Google Scholar
• Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377:1096–101, 1101 e1091–2.
   PubMed Web of Science ®Google Scholar
• Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: how should we use it? J Trauma Acute Care Surg. 2013;74:1575–86.
   PubMed Web of Science ®Google Scholar
• Pusateri AE, Weiskopf RB, Bebarta V, Butler F, Cestero RF, Chaudry IH, Deal V, Dorlac WC, Gerhardt RT, Given MB, Hansen DR, Hoots WK, Klein HG, Macdonald VW, Mattox KL, Michael RA, Mogford J, Montcalm-Smith EA, Niemeyer DM, Prusaczyk WK, Rappold JF, Rassmussen T, Rentas F, Ross J, Thompson C, Tucker LD. Tranexamic Acid and trauma: current status and knowledge gaps with recommended research priorities. Shock. 2013;39:121–6.
   PubMed Web of Science ®Google Scholar
• Morrison JJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147:113.
   PubMedGoogle Scholar
• Morrison JJ, Ross JD, Dubose JJ, Jansen JO, Midwinter MJ, Rasmussen TE. Association of cryoprecipitate and tranexamic acid with improved survival following wartime injury: findings from the MATTERs II Study. JAMA Surg. 2013;148:218–25.
   PubMed Web of Science ®Google Scholar
• Schochl H, Schlimp C, Maegele M. Tranexamic acid, fibrinogen concentrate and prothrombin complex concentrate: data to support prehospital use? Shock. 2014;41(Suppl 1):44–6.
   PubMed Web of Science ®Google Scholar
• Lipsky AM, Abramovich A, Nadler R, Feinstein U, Shaked G, Kreiss Y, Glassberg E. Tranexamic acid in the prehospital setting: Israel Defense Forces’ initial experience. Injury. 2014;45:66–70.
   PubMed Web of Science ®Google Scholar
• Vu EN, Schlamp RS, Wand RT, Kleine-Deters GA, Vu MP, Tallon JM. Prehospital use of tranexamic acid for hemorrhagic shock in primary and secondary air medical evacuation. Air Med J. 2013;32:289–92.
   PubMedGoogle Scholar
• Hoffmann C, Falzone E, Donat A, Leclerc T, Donat N, Tourtier JP. In-flight risk of venous thromboembolism and use of tranexamic acid in trauma patients. Air Med J. 2014;33:48.
   PubMedGoogle Scholar
• Department of Defense. Program Announcement: Tranexamic Acid Clniical Research. Funding opportunity number: W81XWH-12-CCCJPC-TACR. Available at: file:///D:/ Trauma/Trauma%20Research/STAAMP/program%20announ cement%20-%20tacr.pdf. Accessed: March 13, 2014.
   Google Scholar
• Study of Tranexamic Acid during Air Medical Prehospital transport (STAAMP) trial. NCT02086500. Available at: www.clinicaltrials.gov/ct2/show/record/NCT02086500. Acc- essed: March 13, 2014.
   Google Scholar
• de Guzman R, Polykratis IA, Sondeen JL, Darlington DN, Cap AP, Dubick MA. Stability of tranexamic acid after 12-week storage at temperatures from –20°C to 50°C. Prehosp Emerg Care. 2013;17:394–400.
   PubMed Web of Science ®Google Scholar
• Maier RV, Bankey P, McKinley B, Freeman B, Harbrecht BG, Johnson JL, Minei JP, Moore EE, Moore F, Nathens AB, Shapiro M, Tompkins RG, West M. Inflammation and the host response to injury, a large-scale collaborative project: patient-oriented research core-standard operating procedures for clinical care: foreward. J Trauma Acute Care Surg. 2005;59: 762–3.
   Web of Science ®Google Scholar
• United States Food and Drug Adminstration. Code of Federal Regulations Title 21: Section 50.24 Eception from informed consent requirements for emergency research. Available at: www. accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm? fr = 50.24. Accessed: March 13, 2014.
   Google Scholar
• Food and Drug Administration. Guidance fo Institutional Review Boards, Clinical Investigators, and Sponsors: Exception from Informed Consent Requirements for Emergency Research. Available at: www.fda.gov/downloads/ regulatoryinformation/guidances/ucm249673.pdf. Accessed: April 9, 2014.
   Google Scholar
• Office for Human Research Protections. Informed Consent Requirements in Emergency Research. Available at: www.hhs.gov/ohrp/policy/hsdc97–01.html. Accessed: April 9, 2014.
   Google Scholar
• Prehospital Air Medical Plasma Trial (PAMPer). NCT01818427. Available at: clinicaltrials.gov/show/NCT01818427. Accessed: July 13, 2013.
   Google Scholar
• Reade MC, Pitt V, Gruen RL. Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities. Shock. 2013;40:160–1.
   PubMed Web of Science ®Google Scholar
• Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American–European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149:818–24.
   PubMed Web of Science ®Google Scholar
• Sauaia A, Moore EE, Johnson JL, Ciesla DJ, Biffl WL, Banerjee A. Validation of postinjury multiple organ failure scores. Shock. 2009;31:438–47.
   PubMed Web of Science ®Google Scholar