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...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.展开更多
Background and purpose NOTCH3 p.R544C mutation accounts for 5%of spontaneous intracerebral haemorrhage(ICH)in East Asian patients.We investigated whether certain CT features are associated with NOTCH3-related ICH.Meth...Background and purpose NOTCH3 p.R544C mutation accounts for 5%of spontaneous intracerebral haemorrhage(ICH)in East Asian patients.We investigated whether certain CT features are associated with NOTCH3-related ICH.Methods Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation.The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation,including burden of white matter lesion(WML),degree of brain atrophy,number of lacunes,prominent juxtacortical WML and prominent lobar lacunes,were analysed by neuroradiologists blinded to the mutation status.Results Of 299 patients with spontaneous ICH(mean age,61 years;male,68%;ICH volumes,14.1±17.8 mL),13 patients(4.3%)carried NOTCH3 p.R544C mutation.The clinical features,haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers.The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML(69.2%vs 17.8%,p<0.001),and the effects were not driven by ageing as seen in patients without mutation.Prominent juxtacortical WML(area under receiver operating characteristic curve=0.76)outperformed the total WML score and prominent lobar lacunes and significantly predicted NOTCH3 p.R544C mutation in a multivariable-adjusted model(OR,20.9;95%CI 4.94 to 88.6).Conclusion In patients with spontaneous ICH,the severity and topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.展开更多
基金Medical Research Future Fund,Australia(APP1152282).
文摘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.
文摘Background and purpose NOTCH3 p.R544C mutation accounts for 5%of spontaneous intracerebral haemorrhage(ICH)in East Asian patients.We investigated whether certain CT features are associated with NOTCH3-related ICH.Methods Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation.The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation,including burden of white matter lesion(WML),degree of brain atrophy,number of lacunes,prominent juxtacortical WML and prominent lobar lacunes,were analysed by neuroradiologists blinded to the mutation status.Results Of 299 patients with spontaneous ICH(mean age,61 years;male,68%;ICH volumes,14.1±17.8 mL),13 patients(4.3%)carried NOTCH3 p.R544C mutation.The clinical features,haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers.The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML(69.2%vs 17.8%,p<0.001),and the effects were not driven by ageing as seen in patients without mutation.Prominent juxtacortical WML(area under receiver operating characteristic curve=0.76)outperformed the total WML score and prominent lobar lacunes and significantly predicted NOTCH3 p.R544C mutation in a multivariable-adjusted model(OR,20.9;95%CI 4.94 to 88.6).Conclusion In patients with spontaneous ICH,the severity and topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.
