Intracerebral hemorrhage (ICH) affects approximately 2 million people in the world every year. Mortality after ICH is ~40% in the first 30 days. Early hematoma growth after ICH is a strong predictor of mortality and poor outcome. Tranexamic acid (TXA) is an inexpensive and widely available antifibrinolytic agent. In intracerebral hemorrhage (ICH) patients treated within 8 hours of stroke onset, intravenous TXA was associated with a modest reduction in hematoma growth and reduced early mortality (TICH2).

Trial design:

• Phase II investigator-initiated randomized, double-blind, placebo-controlled trial of tranexamic acid in spot sign positive patients within 4½ hours of ICH

Trial population:

• N=100, 18 years and older, both males and females. Enrolled across 13 centers in Australia, Finland and Taiwan.
• Inclusion criteria:
• Patients with acute ICH with “spot sign” on the CTA and presenting within 4.5 hours of symptom onset are included.
• Exclusion criteria:
• GCS < 8
• Brainstem ICH
• ICH volume >70cc as measured by ABC/2
• Any venous or arterial thrombotic event within 12 months
• Use of heparin, low-molecular weight heparin, GPIIb/IIIa antagonist, or oral anticoagulation within the previous 14 days, irrespective of laboratory values
• Concurrent or planned treatment with haemostatic agents

Interventions:

• Intravenous tranexamic acid 1000 mg in 100 mL 0.9% NaCl over 10 minutes followed by 1000 mg in 500 mL 0.9% NaCl infusion over 8 hours versus placebo.

Primary endpoints:

• ICH growth by 24±3 hours as defined by either 33% or 6 ml increase from baseline, adjusted for baseline ICH volume.

Secondary endpoints:

• Absolute ICH growth volume by 24±3 hours, adjusted for baseline ICH volume
• Absolute intraventricular hematoma (IVH) growth volume by 24±3 hours, adjusted for baseline IVH volume
• Modified Rankin Scale (mRS) score of 0-4 at 3 months
• Modified Rankin Scale (mRS) score of 0-3 at 3 months
• Categorical shift in mRS at 3 months, subject to the validity of proportional odds assumption

Safety endpoints:

• Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism)
• Death due to any cause by 3 months

Exploratory endpoints:

• From the trial itself, ClinicalTrials.gov, or other sources, what information is given about any exploratory endpoints of the trial? Leave blank if not applicable or no information is given. (Optimal word count for this is xx to xx but there is no limit.) Adjusting outcome variables, ICH growth and mRS at 90 days, based on baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (<3 vs. >3 hours); baseline ICH volume (<30 vs. >30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (>12 vs. 8-12) and age (<70 vs. >70). These analyses are hypothesis generating, as the trial is not powered for them.

Sponsors and collaborators:

• Neuroscience Trials Australia

Related Science:

• Meretoja A, Churilov L, Campbell BC, Aviv RI, Yassi N, Barras C, Mitchell P, Yan B, Nandurkar H, Bladin C, Wijeratne T, Spratt NJ, Jannes J, Sturm J, Rupasinghe J, Zavala J, Lee A, Kleinig T, Markus R, Delcourt C, Mahant N, Parsons MW, Levi C, Anderson CS, Donnan GA, Davis SM. The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial. Int J Stroke. 2014 Jun;9(4):519-24. doi: 10.1111/ijs.12132. Epub 2013 Aug 26.
• Sprigg, N., Flaherty, K., Appleton, J. P., Al-Shahi Salman, R., Bereczki, D., Beridze, M.,...Bath, P. M. (2018). Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet, 391(10135), 2107-2115. doi:10.1016/s0140-6736(18)31033-x

References:

• Presented by: Nawaf Yassi, MBBS BSc (Med) PhD FRACP, International Stroke Conference 2020, Los Angeles, CA
• ClinicalTrials.gov: NCT01702636