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

Abstract

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. ? Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.