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PHILADELPHIA – according to an investigation presented at the annual meeting of the American Academy of Neurology. For patients with TBI and intracranial hemorrhage (ICH), however, treatment with a 2-gram bolus of tranexamic acid within 42 minutes of injury significantly improves the rate of 28-day survival. Tranexamic acid therefore “is the first therapeutic with evidence for benefit in acute TBI,” said Susan Rowell, MD, trauma medical director at Duke University in Durham, North Carolina.
No effective treatment is available for TBI, which is a major cause of death after trauma. In 2010, the CRASH-2 trial (Lancet. 2010 Jul 03;376[9734]:23-32), suggested that tranexamic acid, a lysine analogue that decreases the breakdown of clots, safely reduced the rate of death from hemorrhage in patients with trauma and bleeding. Patients treated within 1 hour of injury were significantly more likely to survive than those treated at 1 hour or more after injury.
Two small, prospective trials failed to show that tranexamic acid reduced in-hospital mortality, improved neurologic function at discharge, or reduced the progression of ICH. A meta-analysis of both trials, however, showed a trend toward a benefit of treatment with this therapy.
A multicenter, prehospital trial
Dr. Rowell and colleagues hypothesized that prehospital administration of tranexamic acid to patients with moderate to severe TBI early after injury would increase the likelihood of a favorable neurologic outcome. Between March 2015 and March 2017, they enrolled 1,280 participants in a multicenter, prehospital trial. Eligible participants had moderate to severe TBI, were not in shock (as evidenced by a systolic blood pressure greater than 90 mm Hg before randomization), and were enrolled within 2 hours of injury.
Patients were randomized to one of three treatment arms and followed for 6 months. The first treatment arm received a 1-gram bolus of tranexamic acid before hospital admission and an 8-hour, 1-gram infusion of tranexamic acid in the hospital. The second arm received a 2-gram bolus of tranexamic acid before hospital admission and a placebo infusion in the hospital. The third arm received a placebo bolus and placebo infusion. Paramedics and participants were blinded to treatment assignment. The trial was conducted at 20 hospitals and 39 emergency medical services agencies in the United States and Canada.
The study’s primary outcome was functional neurologic outcome at 6 months, as measured by the Glasgow Outcomes Scale – Extended (GOSE). The investigators dichotomized results into favorable and poor categories. Other prespecified outcomes included early and late mortality, the disability rating scale (DRS), and progression of ICH.
Treatment was administered early
The researchers identified 1,280 eligible patients, of whom 1,063 were randomized. The modified intention-to-treat analysis included 309 participants in the placebo group, 312 in the bolus-maintenance group (the 1-gram group), and 345 in the bolus-only group (the 2-gram group). The population’s average age was approximately 42 years, and 75% of the sample was male. About half of the patients had a Glasgow Coma Scale score between 3 and 8. Injury severity and prehospital care were similar among the groups.
The researchers provided the drug infusion at an average of 0.7 hours (42 minutes) after injury, “which is actually quite early,” said Dr. Rowell. They observed few infusion-related deviations, and the entire bolus was infused in about 95% of patients. Approximately 70% of patients received the full 8-hour infusion. This result was influenced partly by stopping rules and by providers who requested unblinding to give open-label tranexamic acid. Overall, 57% of patients in the trial had an ICH on head CT, which was approximately the proportion that the researchers had anticipated.
Dr. Rowell and colleagues completed the 6-month follow-up for 85% of patients. They saw no difference in the 6-month neurologic outcome between the group of all patients who received tranexamic acid and those who received placebo. The investigators also saw no differences between groups in early and late mortality and the DRS.
About half of patients with ICH were evaluated for progression. Progression occurred in 20% of the placebo arm, 17% of the bolus-maintenance arm, and 15% of the bolus-only arm. The differences between groups were not statistically significant. Participants in the bolus-only group, however, were significantly less likely to die, compared with the placebo and the bolus-maintenance groups. The odds ratio of death for the bolus-only group, compared with the others, was about 0.5. The absolute mortality rate for the placebo and bolus-maintenance groups was 17%, compared with 12% for the bolus-only group. Most deaths were attributable to TBI, and few patients died of exsanguination.
In addition, the bolus-only group also had improved long-term neurologic outcome, as assessed by the 6-month DRS and the 6-month GOSE, compared with the bolus maintenance group.
Among patients with ICH, survival increased by approximately 12% at 10 hours after injury in the bolus-only group, compared with the bolus-maintenance and placebo groups. This difference persisted throughout the follow-up period, said Dr. Rowell.
Among predefined major adverse events, seizure-like activity occurred in 5% of the bolus-only group, compared with 2% of the placebo and bolus-maintenance groups. The researchers found no significant differences in any thrombotic event between the bolus-only group and the placebo group.
The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
SOURCE: Rowell S et al. AAN 2019, Abstract.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Academy of Neurology. For patients with TBI and intracranial hemorrhage (ICH), however, treatment with a 2-gram bolus of tranexamic acid within 42 minutes of injury significantly improves the rate of 28-day survival. Tranexamic acid therefore “is the first therapeutic with evidence for benefit in acute TBI,” said Susan Rowell, MD, trauma medical director at Duke University in Durham, North Carolina.
No effective treatment is available for TBI, which is a major cause of death after trauma. In 2010, the CRASH-2 trial (Lancet. 2010 Jul 03;376[9734]:23-32), suggested that tranexamic acid, a lysine analogue that decreases the breakdown of clots, safely reduced the rate of death from hemorrhage in patients with trauma and bleeding. Patients treated within 1 hour of injury were significantly more likely to survive than those treated at 1 hour or more after injury.
Two small, prospective trials failed to show that tranexamic acid reduced in-hospital mortality, improved neurologic function at discharge, or reduced the progression of ICH. A meta-analysis of both trials, however, showed a trend toward a benefit of treatment with this therapy.
A multicenter, prehospital trial
Dr. Rowell and colleagues hypothesized that prehospital administration of tranexamic acid to patients with moderate to severe TBI early after injury would increase the likelihood of a favorable neurologic outcome. Between March 2015 and March 2017, they enrolled 1,280 participants in a multicenter, prehospital trial. Eligible participants had moderate to severe TBI, were not in shock (as evidenced by a systolic blood pressure greater than 90 mm Hg before randomization), and were enrolled within 2 hours of injury.
Patients were randomized to one of three treatment arms and followed for 6 months. The first treatment arm received a 1-gram bolus of tranexamic acid before hospital admission and an 8-hour, 1-gram infusion of tranexamic acid in the hospital. The second arm received a 2-gram bolus of tranexamic acid before hospital admission and a placebo infusion in the hospital. The third arm received a placebo bolus and placebo infusion. Paramedics and participants were blinded to treatment assignment. The trial was conducted at 20 hospitals and 39 emergency medical services agencies in the United States and Canada.
The study’s primary outcome was functional neurologic outcome at 6 months, as measured by the Glasgow Outcomes Scale – Extended (GOSE). The investigators dichotomized results into favorable and poor categories. Other prespecified outcomes included early and late mortality, the disability rating scale (DRS), and progression of ICH.
Treatment was administered early
The researchers identified 1,280 eligible patients, of whom 1,063 were randomized. The modified intention-to-treat analysis included 309 participants in the placebo group, 312 in the bolus-maintenance group (the 1-gram group), and 345 in the bolus-only group (the 2-gram group). The population’s average age was approximately 42 years, and 75% of the sample was male. About half of the patients had a Glasgow Coma Scale score between 3 and 8. Injury severity and prehospital care were similar among the groups.
The researchers provided the drug infusion at an average of 0.7 hours (42 minutes) after injury, “which is actually quite early,” said Dr. Rowell. They observed few infusion-related deviations, and the entire bolus was infused in about 95% of patients. Approximately 70% of patients received the full 8-hour infusion. This result was influenced partly by stopping rules and by providers who requested unblinding to give open-label tranexamic acid. Overall, 57% of patients in the trial had an ICH on head CT, which was approximately the proportion that the researchers had anticipated.
Dr. Rowell and colleagues completed the 6-month follow-up for 85% of patients. They saw no difference in the 6-month neurologic outcome between the group of all patients who received tranexamic acid and those who received placebo. The investigators also saw no differences between groups in early and late mortality and the DRS.
About half of patients with ICH were evaluated for progression. Progression occurred in 20% of the placebo arm, 17% of the bolus-maintenance arm, and 15% of the bolus-only arm. The differences between groups were not statistically significant. Participants in the bolus-only group, however, were significantly less likely to die, compared with the placebo and the bolus-maintenance groups. The odds ratio of death for the bolus-only group, compared with the others, was about 0.5. The absolute mortality rate for the placebo and bolus-maintenance groups was 17%, compared with 12% for the bolus-only group. Most deaths were attributable to TBI, and few patients died of exsanguination.
In addition, the bolus-only group also had improved long-term neurologic outcome, as assessed by the 6-month DRS and the 6-month GOSE, compared with the bolus maintenance group.
Among patients with ICH, survival increased by approximately 12% at 10 hours after injury in the bolus-only group, compared with the bolus-maintenance and placebo groups. This difference persisted throughout the follow-up period, said Dr. Rowell.
Among predefined major adverse events, seizure-like activity occurred in 5% of the bolus-only group, compared with 2% of the placebo and bolus-maintenance groups. The researchers found no significant differences in any thrombotic event between the bolus-only group and the placebo group.
The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
SOURCE: Rowell S et al. AAN 2019, Abstract.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Academy of Neurology. For patients with TBI and intracranial hemorrhage (ICH), however, treatment with a 2-gram bolus of tranexamic acid within 42 minutes of injury significantly improves the rate of 28-day survival. Tranexamic acid therefore “is the first therapeutic with evidence for benefit in acute TBI,” said Susan Rowell, MD, trauma medical director at Duke University in Durham, North Carolina.
No effective treatment is available for TBI, which is a major cause of death after trauma. In 2010, the CRASH-2 trial (Lancet. 2010 Jul 03;376[9734]:23-32), suggested that tranexamic acid, a lysine analogue that decreases the breakdown of clots, safely reduced the rate of death from hemorrhage in patients with trauma and bleeding. Patients treated within 1 hour of injury were significantly more likely to survive than those treated at 1 hour or more after injury.
Two small, prospective trials failed to show that tranexamic acid reduced in-hospital mortality, improved neurologic function at discharge, or reduced the progression of ICH. A meta-analysis of both trials, however, showed a trend toward a benefit of treatment with this therapy.
A multicenter, prehospital trial
Dr. Rowell and colleagues hypothesized that prehospital administration of tranexamic acid to patients with moderate to severe TBI early after injury would increase the likelihood of a favorable neurologic outcome. Between March 2015 and March 2017, they enrolled 1,280 participants in a multicenter, prehospital trial. Eligible participants had moderate to severe TBI, were not in shock (as evidenced by a systolic blood pressure greater than 90 mm Hg before randomization), and were enrolled within 2 hours of injury.
Patients were randomized to one of three treatment arms and followed for 6 months. The first treatment arm received a 1-gram bolus of tranexamic acid before hospital admission and an 8-hour, 1-gram infusion of tranexamic acid in the hospital. The second arm received a 2-gram bolus of tranexamic acid before hospital admission and a placebo infusion in the hospital. The third arm received a placebo bolus and placebo infusion. Paramedics and participants were blinded to treatment assignment. The trial was conducted at 20 hospitals and 39 emergency medical services agencies in the United States and Canada.
The study’s primary outcome was functional neurologic outcome at 6 months, as measured by the Glasgow Outcomes Scale – Extended (GOSE). The investigators dichotomized results into favorable and poor categories. Other prespecified outcomes included early and late mortality, the disability rating scale (DRS), and progression of ICH.
Treatment was administered early
The researchers identified 1,280 eligible patients, of whom 1,063 were randomized. The modified intention-to-treat analysis included 309 participants in the placebo group, 312 in the bolus-maintenance group (the 1-gram group), and 345 in the bolus-only group (the 2-gram group). The population’s average age was approximately 42 years, and 75% of the sample was male. About half of the patients had a Glasgow Coma Scale score between 3 and 8. Injury severity and prehospital care were similar among the groups.
The researchers provided the drug infusion at an average of 0.7 hours (42 minutes) after injury, “which is actually quite early,” said Dr. Rowell. They observed few infusion-related deviations, and the entire bolus was infused in about 95% of patients. Approximately 70% of patients received the full 8-hour infusion. This result was influenced partly by stopping rules and by providers who requested unblinding to give open-label tranexamic acid. Overall, 57% of patients in the trial had an ICH on head CT, which was approximately the proportion that the researchers had anticipated.
Dr. Rowell and colleagues completed the 6-month follow-up for 85% of patients. They saw no difference in the 6-month neurologic outcome between the group of all patients who received tranexamic acid and those who received placebo. The investigators also saw no differences between groups in early and late mortality and the DRS.
About half of patients with ICH were evaluated for progression. Progression occurred in 20% of the placebo arm, 17% of the bolus-maintenance arm, and 15% of the bolus-only arm. The differences between groups were not statistically significant. Participants in the bolus-only group, however, were significantly less likely to die, compared with the placebo and the bolus-maintenance groups. The odds ratio of death for the bolus-only group, compared with the others, was about 0.5. The absolute mortality rate for the placebo and bolus-maintenance groups was 17%, compared with 12% for the bolus-only group. Most deaths were attributable to TBI, and few patients died of exsanguination.
In addition, the bolus-only group also had improved long-term neurologic outcome, as assessed by the 6-month DRS and the 6-month GOSE, compared with the bolus maintenance group.
Among patients with ICH, survival increased by approximately 12% at 10 hours after injury in the bolus-only group, compared with the bolus-maintenance and placebo groups. This difference persisted throughout the follow-up period, said Dr. Rowell.
Among predefined major adverse events, seizure-like activity occurred in 5% of the bolus-only group, compared with 2% of the placebo and bolus-maintenance groups. The researchers found no significant differences in any thrombotic event between the bolus-only group and the placebo group.
The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
SOURCE: Rowell S et al. AAN 2019, Abstract.
REPORTING FROM AAN 2019
Key clinical point: Early administration of tranexamic acid after TBI does not improve neurologic outcome at 6 months.
Major finding: Patients with TBI and ICH who received a 2-g bolus of tranexamic acid had a 50% lower rate of mortality.
Study details: A multicenter, prehospital trial that enrolled 1,063 patients with moderate to severe TBI.
Disclosures: The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
Source: Rowell S et al. AAN 2019, Abstract.