Corresponding Author: Susan Rowell, MD, MBA, Division of Trauma and Critical Care Surgery, Department of Surgery, Duke University School of Medicine, 2301 Erwin Rd, Durham, NC 27707 (susan.rowell@duke.edu).
Accepted for Publication: May 8, 2020.
Correction: This article was corrected on October 27, 2020, to correct Table 2 to indicate the number of participants in the bolus only group that had more than 3% of clot lysed at 30 minutes following maximum amplitude as 31. The Table has been corrected and now indicates 31 participants.
Author Contributions: Dr McKnight and Mr Meier had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Rowell, McKnight, Kannas, May, Sheehan, Bulger, Christenson, Morrison, Colella, Weisfeldt, Zielinski, Auderheide, Williams, Schreiber.
Acquisition, analysis, or interpretation of data: Rowell, Meier, McKnight, Kannas, May, Bulger, Idris, Morrison, Frascone, Bosarge, Colella, Johannigman, Cotton, Callum, McMullan, Dries, Tibbs, Richmond, Tallon, Garrett, Auderheide, Gandhi, Schlamp, Robinson, Jui, Klein, Rizoli, Gamber, Fleming, Hwang, Vincent, Hendrickson, Simonson, Klotz, Sopko, Witham, Ferrara, Schreiber.
Drafting of the manuscript: Rowell, Meier, McKnight, Cotton, Garrett, Zielinski, Auderheide, Schlamp, Robinson, Fleming, Simonson, Sopko, Schreiber.
Critical revision of the manuscript for important intellectual content: Rowell, Meier, McKnight, Kannas, May, Sheehan, Bulger, Idris, Christenson, Morrison, Frascone, Bosarge, Colella, Johannigman, Cotton, Callum, McMullan, Dries, Tibbs, Richmond, Weisfeldt, Tallon, Garrett, Zielinski, Auderheide, Gandhi, Schlamp, Robinson, Jui, Klein, Rizoli, Gamber, Hwang, Vincent, Williams, Hendrickson, Klotz, Sopko, Witham, Ferrara, Schreiber.
Statistical analysis: Meier, McKnight, May, Hwang, Simonson.
Obtained funding: Rowell, McKnight, Kannas, May, Idris, Christenson, Weisfeldt, Schreiber.
Administrative, technical, or material support: Kannas, Sheehan, Bulger, Christenson, Frascone, Bosarge, Callum, McMullan, Dries, Tibbs, Richmond, Weisfeldt, Tallon, Gandhi, Schlamp, Robinson, Jui, Gamber, Williams, Hendrickson, Simonson, Witham, Ferrara, Schreiber.
Supervision: McKnight, Kannas, May, Christenson, Bosarge, Colella, Cotton, Callum, Tibbs, Weisfeldt, Garrett, Zielinski, Schlamp, Robinson, Gamber, Klotz, Schreiber.
Other - conducting the study at St Michael's Hospital in Toronto: Rizoli.
Other - supervised the implementation of the randomized trial in my site (University of Toronto): Morrison.
Other - patient enrolment and site PI: Callum.
Conflict of Interest Disclosures: Dr Rowell reported receiving grants from the US Department of Defense (DoD) and the National Institutes of Health (NIH) during the conduct of the study and personal fees from Portola Phamaceuticals outside the submitted work. Dr McKnight reported receiving grants from DoD and NIH during the conduct of the study. Dr May reported receiving grants from DoD and NIH during the conduct of the study. Dr Sheehan reported receiving grants from DoD and NIH during the conduct of the study. Dr Bulger reported receiving grants from NIH during the conduct of the study. Dr Idris reported receiving grants from NIH during the conduct of the study. Dr Christenson reported receiving grants from NIH during the conduct of the study. Dr Morrison reported receiving grants from NIH, the Canadian Institutes of Health Research, and the Heart and Stroke Foundation Canada during the conduct of the study and endowed chair salary support from the Robert and Dorothy Pitts Chair in Acute Care and Emergency Medicine outside the submitted work. Dr Frascone reported receiving grants from DoD and NIH during the conduct of the study. Dr Bosarge reported receiving grants from DoD during the conduct of the study and personal fees from Avanos outside the submitted work. Dr Cotton reported receiving grants from DoD during the conduct of the study. Dr Callum reported receiving grants from Octapharma and the Canadian Blood Services outside the submitted work. Dr McMullan reported receiving grants from NIH during the conduct of the study. Dr Dries reported receiving grants from DoD and NIH during the conduct of the study. Dr Tibbs reported receiving grants from NIH during the conduct of the study. Dr Weisfeldt reported receiving grants from Johns Hopkins University during the conduct of the study. Dr Auderheide reported receiving grants from the Medical College of Wisconsin during the conduct of the study. Dr Schlamp reported receiving wages paid for duties rendered as a research assistant for the purpose of this trial from the Resuscitation Outcomes Consortium. Dr Williams reported receiving grants from DoD during the conduct of the study. Dr Klotz reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Schreiber reported receiving grants from DoD, NIH, Health Canada, and the American Heart Association and personal fees from Haemonetics during the conduct of the study and personal fees from CSL Behring, Tricol, Velico Medical, and Arsenal Medical outside the submitted work. No other disclosures were reported.
Funding/Support: The Resuscitation Outcomes Consortium institutions participating in the trial were supported by a series of cooperative agreements from the National Heart, Lung and Blood Institute administered by the US Army Medical Research & Material Command (W81XWH-13-2-0090), including U01 HL077863 (University of Washington Data Coordinating Center), U01 HL077866 (Medical College of Wisconsin), U01 HL077871 (University of Pittsburgh), U01 HL077873 (Oregon Health and Science University), U01 HL077881 (University of Alabama at Birmingham), and U01 HL077887 (University of Texas Southwestern Medical Center/Dallas).
Role of the Funder/Sponsors: The US Army Medical Research & Material Command and the National Heart, Lung, and Blood Institute had input in the study design but had no role in the study conduct; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. However, Dr Sopko and Dr Pearson are employed by the National Heart, Lung, and Blood Institute and participated in the review and approval of the manuscript. The American Heart Association has also cosponsored Resuscitation Outcome Consortium research activities and did not participate in any of the above or influence the decision to publish the manuscript.
Group Information: The Resuscitation Outcome Consortium Investigators are listed in the eAppendix in Supplement 2.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of DoD, the National Heart, Lung and Blood Institute, or NIH and should not be construed as an official DoD/US Army policy unless designated by other documentation. No official endorsement should be made.
Meeting Presentations: This study was presented at the Military Health Systems Research Symposium; August 22, 2018, Orlando, Florida; at the American Academy of Neurology Plenary Session; May 5, 2019; Philadelphia, Pennsylvania; and at the TXA in Trauma Symposium; July 5, 2019; Melbourne, Australia.
Data Sharing Statement: See Supplement 3.
1.Feigin
VL , Nichols
E , Alam
T ,
et al; GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.
Lancet Neurol. 2019;18(5):459-480. doi:
10.1016/S1474-4422(18)30499-XPubMedGoogle ScholarCrossref 2.Peterson
AB , Xu
L , Daugherty
J , Breiding
MJ . Surveillance Report of Traumatic Brain Injury-related Emergency Department Visits, Hospitalizations, and Deaths—United States, 2014. Centers for Disease Control and Prevention, US Dept of Health and Human Services; 2019.
6.Kobayashi
T , Sugiura
J . The effect of a new potent antifibrinolytic agent, tranexamic acid.
J Jpn Obstet Gynecol Soc. 1966;13(3):158-167.
PubMedGoogle Scholar 9.Shakur
H , Roberts
I ,
et al. 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(9734):23-32. doi:
10.1016/S0140-6736(10)60835-5Google ScholarCrossref 10.CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.
Lancet. 2019;394(10210):1713-1723. doi:
10.1016/S0140-6736(19)32233-0PubMedGoogle ScholarCrossref 11.CRASH-2 Collaborators. Intracranial Bleeding Study C-2 C (Intracranial B. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study).
BMJ. 2011;343:d3795. doi:
10.1136/bmj.d3795Google ScholarCrossref 13.Clifton
GL , Kreutzer
JS , Choi
SC ,
et al. Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury.
Neurosurgery. 1993;33(1):34-38.
PubMedGoogle Scholar