Prehospital TXA for TBI Trial
Prehospital TXA for TBI Trial
Doente / População Intervenção / Exposição Comparação Desfecho
In 966 patients with moderate or severe traumatic brain injury, out-of-hospital tranexamic acid did not improve 6-month neurologic outcome compared with placebo.
N
966
Desenho
Multicenter, double-blind, placebo-controlled phase 2 randomized clinical trial at 20 trauma centers and 39 EMS agencies in the US and Canada (May 2015 to November 2017) under Exception From Informed Consent. Out-of-hospital patients aged >=15 years with suspected TBI, Glasgow Coma Scale score <=12 and systolic blood pressure >=90 mm Hg were randomized 1:1:1 within 2 hours of injury to tranexamic acid 1 g bolus plus 1 g in-hospital 8-hour infusion (bolus maintenance, n=312), tranexamic acid 2 g bolus plus placebo infusion (bolus only, n=345), or placebo bolus plus placebo infusion (n=309). Of 1063 randomized, 96 received no study drug and 1 was excluded, leaving 966 in the analysis population (mean age 42 years, 74% male, mean out-of-hospital GCS 8, predominantly blunt trauma, median injury-to-drug time 40-43 minutes); 819 (84.8%) had 6-month primary outcome data. Asymmetric significance thresholds: 0.1 for benefit, 0.025 for harm.
Desfecho
Primary: favorable neurologic function at 6 months, defined as Glasgow Outcome Scale-Extended score >4 (moderate disability or good recovery), in the combined tranexamic acid groups vs placebo. Reported secondary end points: 28-day mortality, 6-month Disability Rating Scale score, progression of intracranial hemorrhage, seizures, thromboembolic events.
ResultadoFavorable 6-month neurologic outcome occurred in 65% with tranexamic acid vs 62% with placebo (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) - no significant benefit. No significant differences in 28-day mortality (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). Seizures occurred in 5% of the bolus-only group vs 2% bolus maintenance and 2% placebo; thromboembolic events in 9% bolus only, 4% bolus maintenance and 10% placebo.
Rowell SE, Meier EN, McKnight B, et al. 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;324(10):961-974. 10.1001/jama.2020.8958