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

Abstract

Hemorrhage and coagulopathy remain major drivers of early preventable mortality in military and civilian trauma. The development of trauma-induced coagulopathy and hyperfibrinolysis is associated with poor outcomes. Interest in the use of tranexamic acid (TXA) in hemorrhaging patients as an antifibrinolytic agent has grown recently. Additionally, several reports describe immunomodulatory effects of TXA that may confer benefit independent of its antifibrinolytic actions. A large trial demonstrated a mortality benefit for early TXA administration in patients at risk for hemorrhage; however, questions remain about the applicability in developed trauma systems and the mechanism by which TXA reduces mortality. We describe here the rationale, design, and challenges of the Study of Tranexamic Acid during Air Medical Prehospital transport (STAAMP) trial. The primary objective is to determine the effect of prehospital TXA infusion during air medical transport on 30-day mortality in patients at risk of traumatic hemorrhage. This study is a multicenter, placebo-controlled, double-blind, randomized clinical trial. The trial will enroll trauma patients with hypotension and tachycardia from 4 level I trauma center air medical trans- port programs. It includes a 2-phase intervention, with a prehospital and in-hospital phase to investigate multiple dosing regimens. The trial will also explore the effects of TXA on the coagulation and inflammatory response following injury. The trial will be conducted under exception for informed consent for emergency research and thus required an investigational new drug approval from the U.S. Food and Drug Administration as well as a community consultation process. It was designed to address several existing knowledge gaps and research priorities regarding TXA use in trauma.

Red Blood Cell Storage Duration and Trauma

“…The inclusion criteria were trauma with significant hemorrhage or at risk for significant hemorrhage within 8 hours of injury. Questions have arisen about the applicability of the CRASH-2 RCT results and have prompted additional tranexamic acid studies in specific groups of trauma patients, including the retrospective MATTERs (Military Application Of Tranexamic Acid for Trauma Emergency Resuscitation study; NCT02187120) [37]; the multicenter PATCH RCT (Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage; NCT02187120), which is currently underway and led by investigators at the Trauma Service, The Alfred Hospital, Melbourne, Australia [34,38]; and the multicenter STAAMP RCT (Study of Tranexamic Acid during Air Medical Prehospital Transport; NCT02086500) [39] being led by investigators at the University of Pittsburgh, Pennsylvania. Both the PATCH and STAAMP RCTs will use more defined patient selection criteria to limit heterogeneity of injury severity, which, in turn, allows a manageable and feasible enrollment size of less than 1200 patients.…”

Taking the Blood Bank to the Field: The Design and Rationale of the Prehospital Air Medical Plasma (PAMPer) Trial

“…29 Our group is also leading a trial to examine the effects of prehospital administration of tranexamic acid in trauma patients. 30 Finally, the identification of early platelet dysfunction is a key new area of investigation in TIC research. Platelets play a key role not only in the hemostatic response following injury but also as inflammatory sentinels, serving to activate other immune cell types at the site of injury.…”

Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study

“…Historically, paramedics have not had access to medications that specifically assist in the treatment of hemorrhagic shock secondary to trauma 6,8. However, evidence suggests that early treatment of acute coagulopathies and hemorrhagic shock may significantly reduce preventable death 6,9–11…”