Background The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated th...Background The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/ medium vessel occlusion beyond 4.5- hour time window. Methods The CHinese Acute tissue- Based imaging selection for Lysis In Stroke- Tenecteplase was an investigator- initiated, umbrella phase IIa, open- label, blinded- endpoint, Simon’s two- stage randomised clinical trial in 13 centres across China's Mainland. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/ kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis. Results A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon’s two- stage design. Discussion Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety.展开更多
基金National Key R&D Program of China(2017YFC1308201)Clinical Research Plan of SHDC(SHDC2020CR1041B)Shanghai Municipal Key Clinical Specialty(shslczdzk06102).
文摘Background The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/ medium vessel occlusion beyond 4.5- hour time window. Methods The CHinese Acute tissue- Based imaging selection for Lysis In Stroke- Tenecteplase was an investigator- initiated, umbrella phase IIa, open- label, blinded- endpoint, Simon’s two- stage randomised clinical trial in 13 centres across China's Mainland. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/ kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis. Results A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon’s two- stage design. Discussion Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety.
