FVIIa for Acute hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial

项目摘要 重组因子VIIa治疗急性出血性卒中最早给药时间(FAST)试验 是一项随机、双盲、对照的全球rFVIIa加最佳标准疗法与最佳标准疗法的试验 对脑出血(ICH)患者进行单独治疗。我们的中心假设是，用 在适当选择的自发性脑出血患者发病2小时内rFVIIa可改善预后 以90天时与安慰剂组比较的改良Rankin量表(MRS)的顺序分布来衡量。 我们将在100个医院地点和至少15个移动卒中单元招募的860名患者中测试我们的假设 (MSU)在NINDS StrokeNet(70个站点)和主要的全球机构(30个站点)内 脑出血患者有能力在发病后2小时内进行治疗。参与的国家包括美国、加拿大、 英国、德国、西班牙、日本和澳大利亚。我们将包括体积为60毫升的主题， 无脑室内出血或少量脑室出血(脑室出血评分≤7)，年龄≤80，GCS≥8，并接受治疗 在最后一次已知正常的120分钟内。为了最大限度地减少治疗时间，研究将使用例外情况 知情同意和MSU，目标是在90分钟内完成治疗的患者的1/2 NINDS t-PA试验。我们将在3年半的时间里招募860名患者，并以双盲的方式将他们随机分组 时尚给rFVIIa 80微克/公斤剂量(最大8 mg剂量)或安慰剂。双臂中的受试者将会收到 根据已公布的AHA关于脑出血的指南，最佳药物治疗包括140毫米的目标血压 HG。主要的疗效结果衡量标准是第90天MRS的顺序分布。一次安全 结果将包括缺血事件(脑梗塞、心肌梗死和肺血栓) 在服药学习的4天内。为了测量ICH和IVH的增长，所有受试者都将有基线的非 对比CT和24小时扫描结果。将对ICH、IVH和水肿进行集中容量测量 两个时间点。审判的总体主要调查人员包括约瑟夫·布罗德里克、詹姆斯·格罗塔、 Andrew Naidech和Jordan Elm(主要统计PI)以及每个参与调查的非美国国家/地区的PI。 总而言之，FAST的目标是找到第一种经过科学证明的治疗急性脑出血的方法。

Project Summary Recombinant Factor VIIa (rFVIIa) for Acute hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial is a randomized, double-blind, controlled global trial of rFVIIa plus best standard therapy vs. best standard therapy alone for patients with intracerebral hemorrhage (ICH). Our central hypothesis is that treatment with rFVIIa within two hours of onset in appropriately selected patients with spontaneous ICH improves outcome as measured by the ordinal distribution of the modified Rankin Scale (mRS) at 90 days, as compared to placebo. We will test our hypothesis in 860 patients recruited at 100 hospital sites and at least 15 mobile stroke units (MSUs) within the NINDS StrokeNet (70 sites) and key global institutions (30 sites) with large volumes of patients with ICH and ability to treat within 2 hours of onset. Participating countries include the U.S., Canada, United Kingdom, Germany, Spain, Japan, and Australia. We will include subjects with a volume of ICH < 60 cc, no intraventricular hemorrhage (IVH) or a small volume of IVH (IVH score ≤ 7), age ≤ 80, GCS ≥ 8, and treated within 120 minutes from last known normal. To minimize time-to-treatment, the study will use exception from informed consent and MSUs with a goal of ½ of patients treated within 90 minutes as accomplished in the NINDS t-PA trials. We will recruit the 860 patients over 3 1/2 years and randomize them in a double-blinded fashion to rFVIIa 80 micrograms/kg dose (maximum 8mg dose) or placebo. Subjects in both arms will receive best medical therapy as per published AHA Guidelines for ICH, including a target blood pressure of 140 mm Hg. The primary efficacy outcome measure is the ordinal distribution of the mRS at 90 days. Primary safety outcomes will include ischemic events (cerebral infarction, myocardial infarction, and pulmonary embolus) within 4 days of study medication. To measure growth of ICH and IVH, all subjects will have baseline non- contrast CT and at 24 hours. Centralized volumetric measurements of ICH, IVH, and edema will be done for both time-points. The overall principal investigators (PIs) for the Trial include Joseph Broderick, James Grotta, Andrew Naidech, and Jordan Elm (primary statistical PI) as well as PIs for each participating non-U.S. country. In summary, the goal of FAST is to find the first scientifically proven treatment for acute ICH.