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

IV rt-PA（Activase <$）成为第一个经科学证实和FDA批准的治疗急性缺血性心脏病的药物。 中风（AIS）1996年。尽管rt-PA在急性卒中治疗中取得了进展，但50%的患者 接受rt-PA治疗的患者在3个月时有肢体残疾，而静脉注射rt-PA仅能打开 约30-40%的动脉在一个小时的治疗后。因为时间是一个重要的决定因素 急性缺血性卒中的结局，提高早期治疗速度和成功率的新联合方法 动脉再通对于AIS的治疗是必要的。 将糖蛋白（GP）IIb/IIIa拮抗剂添加到纤维蛋白溶解方案中，增加了纤维蛋白溶解的速度， 急性心肌梗死患者动脉再通率和动脉开放率。GP 急性MI中的IIb/IIIa拮抗剂与脑内出血率的增加无关。 增强AIS纤溶的潜力促使我们采用联合方法进行溶解， 依替巴肽和Rt-PA（CLEAR）卒中试验。该试验表明，低剂量rt-PA 加依替巴肽可在症状发作后3小时内安全用于AIS患者。根据著名的 CLEAR中联合用药的安全性，但与标准剂量rt-PA相比缺乏疗效信号 我们建议进行CLEAR-Enhanced Regimen（CLEARER）中风试验。 这项多中心、双盲、随机化安全性研究旨在提供有关风险的数据 GP IIb/IIIa拮抗剂依替巴肽与低剂量静脉注射rt-PA联合治疗100例AIS的获益 患者患者将随机接受静脉低剂量rt-PA和依替巴肽联合治疗方案，或 标准剂量（0.9 mg/kg）rt-PA，比例为3：1。这将导致总共75名患者接受治疗， 联合方案，25例患者接受标准剂量IV rt-PA单药治疗。治疗患者 将依替巴肽和rt-PA与接受标准剂量rt-PA对照方案治疗的患者进行比较， 目前的研究。本研究的主要具体目的是： 1.为了获得依替巴肽增强给药方案在以下患者中的安全性的可靠估计： 与0.6 mg/kg rt-PA联合治疗急性卒中患者， 出现症状的时间 2.确定联合治疗急性缺血性卒中的估计疗效是否需要 进行大型III期随机试验。 3.为了获得数据，使我们能够确定潜在III期试验所需的样本量 将该组合与标准剂量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.