COMBINATION APPROACH TO LYSIS IN ACUTE ISCHEMIC STROKE STUDY

对于急性缺血性卒中，静脉注射（IV）重组组织纤溶酶原激活剂（rt-PA）于1996年成为第一个经过科学验证并获得FDA批准的治疗方法。尽管rt-PA在急性卒中治疗方面取得了进展，但接受rt-PA治疗的患者中有50%在3个月时出现身体残疾，单独IV rt-PA治疗1小时后仅开放约30-40%的动脉。 在急性心肌梗死中，在纤溶方案中加入糖蛋白（GP）IIB/IIIa血小板受体拮抗剂可增加动脉再通速度和动脉开放患者的总体百分比。已报告了一例接受GP IIb/IIIa拮抗剂和rt-PA（动脉内）联合治疗的患者的少量血清。 联合应用依替巴肽和rt-PA治疗急性缺血性卒中，CLEAR Stroke channel.，将是一项多中心、随机、双盲、序贯、剂量递增的安全性研究，研究急性缺血性卒中患者在症状发作3小时内静脉注射依替巴肽和静脉注射低剂量rt-PA的联合用药。主要安全性终点为36小时内症状性ICH的发生率。患者将以3：1的比例随机分配至联合静脉内依替巴肽和低剂量rt-PA方案或标准剂量（0.9 mg/kg）rt-PA方案。 本研究的主要具体目的是： 1.获得依替巴肽联合低剂量rt-PA治疗症状发作3小时内开始治疗的急性卒中患者的安全性的可靠估计。 2. 确定联合治疗急性缺血性卒中的估计疗效是否需要进行III期随机试验。 3. 在接受联合治疗或标准剂量rt-PA治疗的患者中，获得关于24小时内进行的多模式MRI为III期再通试验提供替代终点的潜力的初步数据，包括血管通畅性评价、梗死体积以及出血性转化的定量和定性评估。

For acute ischemic stroke, intravenous (IV) recombinant tissue-Plasminogen Activator (rt-PA) become the first scientifically proven and FDA-approved therapy in 1996. Despite the advance that rt-PA represents for acute stroke therapy, 50% of patients treated with rt-PA have physical disability at three months, and IV rt-PA alone opens only approximately 30-40% of arteries after one hour of treatment. In acute myocardial infarction, the addition of glycoprotein (GP) IIB/IIIa platelet receptor antagonists to fibrinolytic regimens increases the speed of arterial recanalization and the overall percentage of patients with open arteries. One small serum of patients treated with the combination of a GP IIb/IIIa antagonist and rt-PA (intra-arterial) has been reported. The Combination approach to Lysis utilizing Eptifibatide And rt-PA in acute ischemic stroke, The CLEAR Stroke channel., will be a multi-center, randomized, double-blind, sequential, dose-escalation safety study of the combination of IV eptifibatide and IV low-dose rt-PA given to acute ischemic stroke patients within 3 hours of symptom onset. The primary safety endpoint will be the incidence of symptomatic ICH within 36 hours. Patients will be randomized to a combined intravenous eptifibatide and low-dose rt-PA regimen, or a standard dose (0.9 mg/kg) rt-PA regimen in a 3 to 1 ratio. The Primary Specific Aims for this Study are: 1. To obtain reliable estimates of the safety of eptifibatide in combination with low-dose rt-PA in acute stroke patients in whom treatment is begun within three hours of symptom onset. 2. To determine if the estimated efficacy of combination therapy in acute ischemic stroke warrants proceeding to a Phase III randomized trial. 3. To obtain preliminary data regarding the potential of multi-modal MRI performed in 24 hours in providing surrogate endpoints for a phase III recanalization trial, including evaluations of vessel patency, volume of infarction, and quantitative and qualitative assessments of hemorrhagic transformation, in patients treated with combination therapy or standard dose rt-PA.