What is the name of the study for the usage of tranexamic acid (TXA) in non-traumatic intracranial bleeding (ICB)?

Key Studies on Tranexamic Acid in Non-Traumatic Intracranial Hemorrhage

The primary studies examining tranexamic acid in non-traumatic intracranial hemorrhage are the TICH-2 trial and ULTRA trial, though neither demonstrated mortality or functional outcome benefits despite reducing hematoma expansion. 1

Major Clinical Trials

TICH-2 Trial (Spontaneous ICH)

• This was the landmark randomized controlled trial evaluating TXA in spontaneous, non-traumatic intracerebral hemorrhage 1
• The trial showed no significant impact on mortality (RR 1.02,95% CI 0.88-1.19) or poor functional outcomes (RR 0.98,95% CI 0.93-1.04) 1
• Despite reducing hematoma expansion rates, this did not translate into improved clinical outcomes 1, 2
• The American Heart Association/American Stroke Association and European Stroke Organisation both concluded from this evidence that TXA should not be routinely used for spontaneous ICH outside of clinical trials 1

Subarachnoid Hemorrhage Studies

• Multiple trials in aneurysmal SAH demonstrated that TXA reduces rebleeding risk (RR 0.6,95% CI 0.44-0.8) but increases cerebral ischemia/stroke risk (RR 1.29,95% CI 1.01-1.67) 1
• This trade-off between preventing rebleeding and causing ischemic complications has prevented guideline endorsement for routine SAH use 1
• The Neurocritical Care Society notes this increased ischemic risk as a significant safety concern specific to SAH patients 1

Contrast with Traumatic Brain Injury

CRASH-2 IBS and CRASH-3 Trials

• The CRASH-2 Intracranial Bleeding Study was a nested randomized trial within the larger CRASH-2 trauma study, specifically examining TBI patients 3
• CRASH-3 subsequently showed potential benefit in mild-to-moderate traumatic brain injury when given within 3 hours (RR 0.78,95% CI 0.64-0.95) 1
• This traumatic brain injury benefit does NOT extend to non-traumatic ICH, representing a critical distinction in clinical practice 1, 2

Current Evidence Synthesis

• A 2023 meta-analysis confirmed that TXA significantly inhibits hematoma growth in ICH patients (mean difference -1.76,95% CI -2.78 to -0.79) but this radiographic benefit does not improve functional outcomes 4
• The disconnect between reducing hematoma expansion and failing to improve mortality or disability represents the fundamental limitation of TXA in non-traumatic ICH 1, 2

Clinical Implementation Considerations

Patient Selection Issues

• Patients with very large hemorrhages are unlikely to benefit, as further bleeding reduction has minimal impact on already catastrophic injury 1
• The American College of Emergency Physicians emphasizes that if TXA is used, administration must occur within 3 hours of symptom onset, ideally within 1 hour 1
• No major guideline body recommends routine TXA use for non-traumatic ICH, including hypertensive ICH, outside of ongoing clinical trials 1

Ongoing Research

• The International Society on Thrombosis and Haemostasis notes ongoing trials investigating TXA specifically in ICH patients on direct oral anticoagulants 1
• This represents a potential subpopulation where benefits might emerge, but current evidence remains insufficient for routine use 1

Safety Profile

• TXA has not shown significant increases in thromboembolic events across non-traumatic ICH studies 1
• The exception is the increased cerebral ischemia risk specifically in SAH patients 1
• Higher doses are associated with increased seizure risk, particularly noted in cardiac surgery populations 5, 6