Faculty Collaboration Database

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. JAMA 2020 Sep 08;324(10):961-974

Date

09/09/2020

Pubmed ID

32897344

Pubmed Central ID

PMC7489866

DOI

10.1001/jama.2020.8958

Scopus ID

2-s2.0-85090870154 (requires institutional sign-in at Scopus site)   161 Citations

Abstract

IMPORTANCE: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI.

OBJECTIVE: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher.

INTERVENTIONS: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309).

MAIN OUTCOMES AND MEASURES: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events.

RESULTS: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16).

CONCLUSIONS AND RELEVANCE: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01990768.

Author List

Rowell SE, Meier EN, McKnight B, Kannas D, May S, Sheehan K, Bulger EM, Idris AH, Christenson J, Morrison LJ, Frascone RJ, Bosarge PL, Colella MR, Johannigman J, Cotton BA, Callum J, McMullan J, Dries DJ, Tibbs B, Richmond NJ, Weisfeldt ML, Tallon JM, Garrett JS, Zielinski MD, Aufderheide TP, Gandhi RR, Schlamp R, Robinson BRH, Jui J, Klein L, Rizoli S, Gamber M, Fleming M, Hwang J, Vincent LE, Williams C, Hendrickson A, Simonson R, Klotz P, Sopko G, Witham W, Ferrara M, Schreiber MA

Authors

Tom P. Aufderheide MD Professor in the Emergency Medicine department at Medical College of Wisconsin
Mario R. Colella DO, MPH Professor in the Emergency Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Antifibrinolytic Agents
Brain Diseases
Brain Injuries, Traumatic
Double-Blind Method
Emergency Medical Services
Female
Follow-Up Studies
Glasgow Coma Scale
Humans
Infusions, Intravenous
Male
Middle Aged
Neuropsychological Tests
Patient Acuity
Survival Analysis
Time-to-Treatment
Tranexamic Acid