番茄社区

PHILADELPHIA -- Prehospital tranexamic acid (TXA) did not improve neurologic outcomes for patients with acute traumatic brain injury (TBI) in a randomized controlled trial, but it did improve 28-day survival rates for some patients, researchers said here.

Patients administered 1 or 2 g of TXA before entering the hospital were not significantly more likely than the placebo group to show Glasgow Outcome Scale-Extended (GOSE) scores greater than 4 -- the trial's primary endpoint -- at 6 months (OR 0.87, 95% CI 0.65-1.17, P=0.18), reported Susan Rowell MD, MCR, of the Oregon Health & Science University in Portland, and colleagues.

However, among patients with intracranial hemorrhage, the 2-g prehospital TXA dose did improve 28-day mortality compared with the 1-g and placebo groups (OR 0.49, 95% CI 0.26-0.94), she said at the American Academy of Neurology annual meeting.

"In patients with intracranial hemorrhage, while prehospital TXA did not decrease hemorrhage progression, a 2-g bolus of TXA initiated about 42 minutes after injury significantly improved 28-day survival," Rowell said. "It is the first therapeutic evidence for benefit in TBI."

In the , 312 patients received 1 g prehospital TXA followed by 1 g infused in the hospital, while 345 received 2 g prehospital TXA followed by a placebo infusion, and 309 received a placebo at both time points. The primary analysis of GOSE scores combined the first two treatment arms and compared them with placebo. Secondary measures, such as 28-day mortality and safety outcomes, were compared in pairwise analysis.

The current therapy for patients with TBI is mostly supportive, and typically the consequences of the injury are treated, as opposed to the injury itself, said Max Wintermark, MD, of Stanford University in California, who was not involved in this study.

One of the advantages of a therapy that can be infused before hospital admittance is that it could minimize the development of TBI, and allow clinicians to intervene before it progresses to an advanced stage, Wintermark said.

"So far, all of the trials that have been conducted of TBI patients have not lead to any positive results, which is very disappointing," Wintermark told 番茄社区. "It seems this is the first one there is some signal that there might be an effect of treatment that could help patients with TBI."

Rowell said this therapy came into wider use after the demonstrated reduced mortality rates in bleeding trauma patients given TXA. The trial also showed that the timing of TXA administration was critical, as those who received therapy within 1 hour from injury had a much higher chance of surviving than a group that received treatment between 1 and 3 hours after injury.

Since then, TXA has been added to the World Health Organization and has been used in military combat situations, Rowell said.

Overall, 1,063 patients with moderate to severe TBI were randomized to the three groups across 12 sites in the U.S. and Canada. Patients were required to be enrolled within 2 hours after their injury, and excluded if they were in shock. FDA requirements for informed consent were waived so patients could be enrolled through emergency medical services in the field.

Patients (three-quarters men; mean age 42) had Glasgow Coma Scale scores of 3 to 8. The injury severity and prehospital care was similar across groups, and there were few penetrating injuries, Rowell noted. More than 90% of study participants had the entire initial dose infused.

A few patients had seizures and thromboembolic events in all groups, the most common of which was thrombotic stroke.

TXA also failed to significantly improve intracranial hemorrhage progression -- defined as >33% increase in total hemorrhage volume -- with 20% of patients in placebo progressing versus 17% in the 1-g prehospital dose group and 15% in the 2-g prehospital dose group.

However, patients with intracranial hemorrhage on their initial CT scan (57%) did also have "important near outcomes" in terms of 6-month Disability Rating Scale (DRS) scores and 6-month favorable GOSE scores when they received TXA versus placebo.

Wintermark noted that there could be certain biomarkers that determine whether this therapy will work in patients, as TBI is not a homogeneous condition.

Rowell said the mechanism behind this association remains unknown, although one possibility was that it worked by strengthening clots and decreasing bleeding.

"Interestingly, when you look at CRASH-2, there was no difference in the number of blood units being transfused," Rowell said. "Similarly in this trial, we saw no difference in intracranial hemorrhage progression, so it is unclear whether that plays a role or not."

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