Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Nawaf Yassi, Henry Zhao, Leonid Churilov, Bruce C V Campbell, Teddy Wu, Henry Ma, Andrew Cheung, Timothy Kleinig, Helen Brown, Philip Choi, Jiann-Shing Jeng, Annemarei Ranta, Hao-Kuang Wang, Geoffrey C Cloud, Rohan Grimley, Darshan Shah, Neil Spratt, Der-Yang Cho, Karim Mahawish, Lauren Sanders, John Worthington, Ben Clissold, Atte Meretoja, Vignan Yogendrakumar, Mai Duy Ton, Duc Phuc Dang, Nguyen Thai My Phuong, Huy-Thang Nguyen, Chung Y Hsu, Gagan Sharma, Peter J Mitchell, Bernard Yan, Mark W Parsons, Christopher Levi, Geoffrey A Donnan, Stephen M Davis

Stroke Vasc Neurol. 2021 Nov 30;svn-2021-001070

 

Rationale: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.

Methods and design: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.

Hypothesis: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.

Sample size estimates: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.

Intervention: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.

Primary efficacy measure: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.

Discussion: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.