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
Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability,with recent positive randomised trials leading to guideline changes worldwide.This review discusses in detail the evidence p...Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability,with recent positive randomised trials leading to guideline changes worldwide.This review discusses in detail the evidence provided by recent randomised trials and metaanalyses,the remaining areas of uncertainty and the future directions for research.The data from existing trials have demonstrated the robust benefit of endovascular thrombectomy for internal carotid and proximal middle cerebral artery occlusions.Uncertainty remains for more distal occlusions where the efficacy of alteplase is greater,less tissue is at risk and the safety of endovascular procedures is less established.Basilar artery occlusion was excluded from the trials,but with a dire natural history and proof of principle that rapid reperfusion is effective,it seems reasonable to continue treating these patients pending ongoing trial results.There has been no evidence of heterogeneity in treatment effect in clinically defined subgroups by age,indeed,those aged>80 years have at least as great an overall reduction in disability and reduced mortality.Similarly there was no heterogeneity across the range of baseline stroke severities included in the trials.Evidence that routine use of general anaesthesia reduces the benefit of endovascular thrombectomy is increasing and conscious sedation is generally preferred unless severe agitation or airway compromise is present.The impact of time delays has become clearer with description of onset to imaging and imaging to reperfusion epochs.Delays in the onset to imaging reduce the proportion of patients with salvageable brain tissue.However,in the presence of favourable imaging,rapid treatment appears beneficial regardless of the onset to imaging time elapsed.Imaging to reperfusion delays lead to decay in the clinical benefit achieved,particularly in those with less robust collateral flow.The brain imaging options to assess prognosis have various advantages and disadvantages,but whatever strategy is employed must be fast.Ongoing trials are investigating extended time windows,using advanced brain imaging selection.There is also a need for further technical advances to maximise rates of complete reperfusion in the minimum time.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Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability,with recent positive randomised trials leading to guideline changes worldwide.This review discusses in detail the evidence provided by recent randomised trials and metaanalyses,the remaining areas of uncertainty and the future directions for research.The data from existing trials have demonstrated the robust benefit of endovascular thrombectomy for internal carotid and proximal middle cerebral artery occlusions.Uncertainty remains for more distal occlusions where the efficacy of alteplase is greater,less tissue is at risk and the safety of endovascular procedures is less established.Basilar artery occlusion was excluded from the trials,but with a dire natural history and proof of principle that rapid reperfusion is effective,it seems reasonable to continue treating these patients pending ongoing trial results.There has been no evidence of heterogeneity in treatment effect in clinically defined subgroups by age,indeed,those aged>80 years have at least as great an overall reduction in disability and reduced mortality.Similarly there was no heterogeneity across the range of baseline stroke severities included in the trials.Evidence that routine use of general anaesthesia reduces the benefit of endovascular thrombectomy is increasing and conscious sedation is generally preferred unless severe agitation or airway compromise is present.The impact of time delays has become clearer with description of onset to imaging and imaging to reperfusion epochs.Delays in the onset to imaging reduce the proportion of patients with salvageable brain tissue.However,in the presence of favourable imaging,rapid treatment appears beneficial regardless of the onset to imaging time elapsed.Imaging to reperfusion delays lead to decay in the clinical benefit achieved,particularly in those with less robust collateral flow.The brain imaging options to assess prognosis have various advantages and disadvantages,but whatever strategy is employed must be fast.Ongoing trials are investigating extended time windows,using advanced brain imaging selection.There is also a need for further technical advances to maximise rates of complete reperfusion in the minimum time.
