Combination approach to Lysis utilizing Eptifibatide And rt-PA -Enhanced Regimen

静脉注射rt-PA(激活酶)成为首个科学证明和FDA批准的治疗急性缺血的药物 1996年中风(AIS)。尽管rt-PA代表着急性中风治疗的进步，但50%的患者 接受rt-PA治疗的患者在三个月后身体残疾，而单独静脉注射rt-PA只能打开 大约30%-40%的动脉在治疗一小时后。因为时间是一个重要的决定因素 急性缺血性卒中的预后：提高早期治疗速度和成功率的新组合方法 动脉再通是治疗AIS的必要手段。 在纤溶方案中加入糖蛋白(GP)Lib/Ila拮抗剂，既提高了 动脉再通和急性心肌梗死患者中动脉开放的百分比。全科医生 急性多发性脑脊液中的LLB/111a拮抗剂与脑出血发生率的增加无关。 在AIS中增强纤溶的潜力使我们进行了联合应用溶栓的方法 依替非那肽和rt-PA(Clear)卒中试验。该试验表明，小剂量rt-PA联合应用 AIS患者可在症状出现后3小时内安全地给予依替非那肽。基于值得注意的 联合用药安全性明确，但与标准剂量rt-PA相比缺乏疗效信号 我们建议进行CLEAR增强方案(CLEAR)卒中试验。 这项多中心、双盲、随机的安全性研究旨在提供有关风险的数据 联合小剂量静脉注射rt-PA治疗100例AIS的益处 病人。患者将随机接受联合静脉注射小剂量rt-PA和依替菲替卡的方案，或 标准剂量(0.9 mg/kg)rt-PA按3：1比例给予。这将导致总共75名患者接受 联合方案治疗25例，单用标准剂量IV型rt-PA治疗。接受治疗的患者 依替菲肽和rt-PA将与标准剂量rt-PA对照组治疗的患者进行比较 目前的研究。这项研究的主要具体目标是： 1.为获得可靠的依替非那肽强化给药方案的安全性评估 联合0.6 mg/kg rt-PA治疗3周内开始治疗的急性脑卒中患者 症状出现的小时数。 2.确定联合治疗急性缺血性卒中的估计疗效是否有根据 进行一项大型的第三阶段随机试验。 3.获得数据，以便我们确定潜在的第三阶段试验所需的样本量 将联合用药与标准剂量rt-PA进行比较。

IV rt-PA (Activase¿) became the first scientifically proven and FDA-approved therapy for acute ischemic stroke (AIS) 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 intravenous rt-PA alone opens only approximately 30-40% of arteries after one hour of treatment. Because time is an important determinant of outcome in acute ischemic stroke, new combination approaches to improve the speed and success of early arterial recanalization are necessary for treatment of AIS. The addition of Glycoprotein (GP) lib/I I la antagonists to fibrinolytic regimens, increase both the speed of arterial recanalization and the percentage of patients with open arteries in acute myocardial infarction. GP llb/llla antagonists in acute Ml have not been associated with increased rates of intracerebral hemorrhage. The potential to augment fibrinolysis in AIS led us to perform the Combined approach to Lysis utilizing Eptifibatide And Rt-PA (CLEAR) stroke trial. That trial demonstrated that the combination of low dose rt-PA plus eptifibatide can be safely given to AIS patients within 3 hours of symptom onset. Based on the notable safety of the combination in CLEAR but the lack of a signal of efficacy compared with standard dose rt-PA we propose to perform the CLEAR-Enhanced Regimen (CLEARER) stroke trial. This multi-center, double-blind, randomized safety study is designed to provide data concerning the risks and benefits of combining a GP llb/llla antagonist, eptifibatide, with low-dose intravenous rt-PA in 100 AIS patients. Patients will be randomized to a combined intravenous low-dose rt-PA and eptifibatide regimen, or standard dose (0.9 mg/kg) rt-PA in a 3 to 1 ratio. This will result in a total of 75 patients treated with a combined regimen, and 25 patients treated with standard dose IV rt-PA alone. Patients treated with eptifibatide and rt-PA will be compared to patients treated with the control regimen of standard dose rt-PA in the present study. The Primary Specific Aims for this Study are: 1. To obtain reliable estimates of the safety of an enhanced dosing regimen of eptifibatide in combination with 0.6 mg/kg of 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 large Phase III randomized trial. 3. To obtain data that will allow us to determine the sample size needed for a potential Phase III trial comparing the combination to standard dose rt-PA.