Poster Presentation Australian and New Zealand Stroke Organisation Conference 2025

Treatment of stroke recurrence in Cerebral Amyloid Angiopathy with Tranexamic Acid (TOSCCAA-TXA): A phase 2 double-blinded randomised controlled clinical trial (Study Protocol).  (#131)

Oshi Swarup 1 2 , Pamela Galindo 1 , Zhibin Chen 2 , Dermot Mallon 3 , Nawaf Yassi 4 , David Werring 3 , Robert L. Medcalf 5 , Geoffrey Cloud 1 2
  1. Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
  2. Department of Clinical Neurosciences, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
  3. The National Hospital for Neurology & Neurosurgery Queen Square, London
  4. Department of Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
  5. Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia

Background/Aims: Cerebral Amyloid Angiopathy (CAA) is a common cause of intracranial haemorrhage (ICH) and is associated with a high risk of subsequent intracranial haemorrhage. CAA is caused by pathologic deposition of amyloid-beta within the vessels of cortical and leptomeningeal arterioles.  Amyloid-beta can provide co-factor activity to promote fibrinolysis by excessive plasmin production leading to increased blood-brain barrier permeability and inflammation in CAA1,2 Tranexamic acid (TXA), an antifibrinolytic agent, inhibits this interaction and may then reduce local plasmin-mediated inflammation and ICH. Our aim is to determine the safety and feasibility of using TXA to reduce ICH recurrence in CAA. We hypothesise that administration of oral TXA will be safe and feasible in CAA-related ICH.

Methods: A multicentre, randomised, double-blinded, placebo-controlled phase IIa clinical trial, funded through Lisla Wellington Stroke Research fund. We aim to recruit 60 patients aged ≥50 years with probable CAA (Boston criteria v2.0) and history of ICH in the preceding 6 months3. Participants will be randomised 1:1 to receive TXA 1g TDS orally or placebo for 6 months, with 12 months follow-up.

Results: Primary outcomes are feasibility (participation and adherence rates) and safety (serious adverse thrombotic events and death). Secondary outcomes include CAA-related intracranial haemorrhage, progression of MRI white matter hyperintensities, brain volume loss, diffusion-weighted ischaemic lesions and changes in cognitive function (Montreal Cognitive Assessment). Recruitment will commence mid- 2025, with anticipated completion by mid-2027.

Conclusion: If feasible and safe, this study will inform a larger phase III trial of a novel secondary preventative strategy for CAA-related ICH.

  1. Mutimer CA, Keragala CB, Markus HS, Werring DJ, Cloud GC, Medcalf RL. Cerebral Amyloid Angiopathy and the Fibrinolytic System: Is Plasmin a Therapeutic Target? Stroke. 2021;52:2707-2714. doi: 10.1161/STROKEAHA.120.033107
  2. Liu Z, McCutcheon FM, Ho H, Chia J, Xiao Y, Tippett I, Keragala CB, Cloud GC, Medcalf RL. Tranexamic acid in a mouse model of cerebral amyloid angiopathy: setting the stage for a novel stroke treatment approach. Res Pract Thromb Haemost. 2023;7:102166. doi: 10.1016/j.rpth.2023.102166
  3. Charidimou A, Boulouis G, Frosch MP, Baron JC, Pasi M, Albucher JF, Banerjee G, Barbato C, Bonneville F, Brandner S, et al. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study. Lancet Neurol. 2022;21:714-725. doi: 10.1016/S1474-4422(22)00208-3