Tranexamic acid is a promising new pharmacological treatment for traumatic brain injury
Traumatic brain injury (TBI) is an injury that occurs in two phases. The primary injury phase refers to the fall, impact, or accelerating/decelerating force that causes TBI, while the secondary injury phase refers to a cascade of cellular changes caused by the initial injury. Secondary injuries are often diverse and may include swelling, intracranial bleeding, changes in blood volume, and diminished oxygen in the brain. These injuries can be severe and life-threatening, so managing secondary TBI is critical for minimizing long-term consequences. Accordingly, secondary TBI is the most common target for researchers who develop interventions to treat TBI.
Recently, researchers used a medication-based intervention to treat the intracranial bleeding that can occur after TBI. To do so, they conducted a large-scale randomized controlled trial to test the effectiveness of a drug called tranexamic acid, which previously has been used to control bleeding during surgery or after physical trauma. The researchers wanted to determine if patients who received tranexamic acid within three hours of TBI were more likely to survive their injuries.
The researchers gathered hospital data from patients who had intracranial bleeding as a result of moderate to severe TBI. Some (4,649) patients received tranexamic acid, while others (4,553) received a placebo treatment within three hours of their initial injury.
The researchers found that patients with moderate TBI who received tranexamic acid were significantly more likely to survive than patients who received the placebo drug. However, there was no statistically significant difference in mortality for patients with severe TBI. They also found that patients with moderate TBI who received treatment within one hour of injury had better outcomes than those that received treatment at about three hours after injury. Again, no such effect was observed in patients with severe TBI. Finally, the researchers found no differences in the level of post-injury disability between patients who received tranexamic acid and those who received the placebo drug.
These findings indicate that tranexamic acid may be effective in reducing the occurrence of TBI-related death for moderate (but not severe) head injury, and that that faster treatment results in improved outcomes.
Several features of this study indicate that these are strong, reliable findings. Because the study was a randomized control trial with a placebo group, the researchers are confident that all of the observable effects are a result of tranexamic acid rather than a result of the placebo effect. Additionally, the results of this study are statistically accurate due to a large sample size, which included nearly 10,000 patients. Finally, the study was conducted across 175 hospitals in 29 countries, and there is no concern that the results were due to specific practices that may occur at a single hospital.
However, like all research studies, this study has limitations. In particular, although the results were statistically significant, the effect sizes were small: in some cases, tranexamic acid only reduced the likelihood of death by about 1 percent compared to placebo treated controls. Additionally, the researchers cannot conclusively determine that tranexamic acid actually reduces intracranial bleeding because the only measured outcome was patient survival. To conclude that this drug effectively treats this secondary injury, the researchers need to gather data specific to mechanisms of intracranial bleeding.
This study presents evidence that rapidly administered tranexamic acid may improve outcomes in patients with moderate TBI. Further research is necessary to determine if this promising drug should be considered a component of standard post-injury practice.
Crash, T. 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. The Lancet. (2019).