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

项目摘要 重组凝血因子VIIa（rFVIIa）治疗急性出血性卒中的早期给药（FASTEST）试验 是一项rFVIIa+最佳标准治疗与最佳标准治疗的随机、双盲、对照全球试验 脑出血（ICH）患者的单独治疗。我们的中心假设是， 在适当选择的自发性ICH患者中，发作2小时内的rFVIIa可改善结局， 与安慰剂相比，通过90天时改良兰金量表（mRS）的有序分布测量。 我们将在100家医院和至少15个移动的卒中单元招募的860名患者中检验我们的假设 在NINDS StrokeNet（70个站点）和主要全球机构（30个站点）内， ICH患者，并且能够在发作后2小时内进行治疗。参与国包括美国、加拿大、 英国、德国、西班牙、日本和澳大利亚。我们将纳入ICH体积< 60 cc的受试者， 无脑室内出血（IVH）或少量IVH（IVH评分≤ 7），年龄≤ 80岁，GCS ≥ 8，并接受治疗 在120分钟内恢复正常为了最大限度地缩短治疗时间，研究将使用例外情况， 知情同意和MSU，目标是在90分钟内完成一半患者的治疗， NINDS t-PA试验。我们将在3年半的时间里招募860名患者，并将他们随机分配到一个双盲研究中。 以rFVIIa 80 μ g/kg剂量（最大8 mg剂量）或安慰剂的方式。两组受试者将接受 根据已发表的AHA ICH指南，最佳药物治疗，包括目标血压140 mm Hg.主要疗效结局指标为90天时mRS的有序分布。主要安全性 结局将包括缺血性事件（脑梗死、心肌梗死和肺栓塞） 研究药物给药后4天内。为了测量ICH和IVH的增长，所有受试者的基线非 CT增强扫描及24小时后复查。将对ICH、IVH和水肿进行集中体积测量， 两个时间点。试验的主要研究者（PI）包括Joseph Broderick，James Grotta， Andrew Naidech和Jordan Elm（主要统计PI）以及每个参与的非美国国家的PI。 总之，FAST的目标是找到第一个经科学证实的治疗急性ICH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.