Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury

Department of Surgery, Oregon Health & Science University, Portland. Department of Surgery, Duke University School of Medicine, Durham, North Carolina. Department of Biostatistics, University of Washington, Seattle. Department of Surgery, University of Washington, Seattle. Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas. Department of Emergency Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Providence Health Care Research Institute, Vancouver, British Columbia, Canada. Rescu, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada. Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Department of Emergency Medicine, Regions Hospital, St Paul, Minnesota. Department of Surgery, University of Alabama, Birmingham. Department of Surgery, University of Arizona, Phoenix. Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee. Department of Surgery, University of Cincinnati, Cincinnati, Ohio. Department of Surgery, McGovern Medical School, University of Texas Health Science Center, Houston. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio. Department of Surgery, Regions Hospital, St Paul, Minnesota. Trauma Surgery, Texas Health Presbyterian Hospital, Dallas. Department of Emergency Medicine, John Peter Smith Health Network, Ft Worth, Texas. Johns Hopkins School of Medicine, Baltimore, Maryland. British Columbia Emergency Health Services, Vancouver, British Columbia, Canada. Department of Emergency Medicine, Baylor University Medical Center, Dallas, Texas. Department of Surgery, Mayo Clinic, Rochester, Minnesota. Department of Surgery, John Peter Smith Health Network, Ft Worth, Texas. Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon. Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota. Department of Surgery, St Michael's Hospital, Toronto, Ontario, Canada. Department of Emergency Medicine, Medical City Plano, Plano, Texas. Emergency Medicine, Methodist Dallas Medical Center, Dallas, Texas. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Trauma Surgery, Texas Health Harris Methodist Hospital, Ft Worth.

Jama. 2020;324(10):961-974
PICO Summary

Population

Out-of-hospital patients with traumatic brain injury aged 15 years or older (n= 1280).

Intervention

Bolus maintenance group: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (n = 312).

Comparison

Bolus only group: out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (n = 345). Placebo group: out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (n = 309).

Outcome

A total of 819 participants were available for primary outcome analysis at 6-month follow-up. The primary outcome (favorable neurologic function at 6 months) occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group. There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%); 6-month Disability Rating Scale score (6.8 vs 7.6); or progression of intracranial hemorrhage (16% vs 20%).
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.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine