Phase IIB Study of TNK in Acute Stroke (TNK-S2B-STAT)

TNK-S2B STAT和TNK-S2B CLIN是独立但高度协调的单元，它们共同提出了一项大型、多中心、随机对照试验，在发病3小时内接受治疗的急性缺血性中风患者中比较TNK和rt-PA。TNK-S2B STAT的目标是：1)提供一个统计设计，确定与RT-PA相比，TNK在减少急性缺血性中风后的不良结果方面是否显示出希望，同时将随访时间和所需患者数量降至最低。2)执行、有效整合并负责秋明-S2B的所有数据管理业务。3)及时向临床协调中心(CCC)传递秋明-S2B项目首席研究员履行其职责所需的所有数据，以确保患者安全和指导所有临床手术。统计分析计划包含几个创新特点： 1)顺序选择程序确定两种剂量(0.1或0.4毫克/公斤)中的一种在24小时内对主要神经改善更好。 2)与rt-PA的初步随机比较评估了选择的TNK剂量是有希望的还是无效的。结果是3个月后的改良Rankin评分。 3)如果TNK是有希望的而不是徒劳的，III期试验将比较TNK与rt-PA，再次与3个月后的改良Rankin评分作为结果。 3)为了提高效率，最初的TNK/RT-PA比较中包括的200名患者将被纳入III期试验(总体n=1908名患者)，如果试验继续进行的话。

TNK-S2B STAT and TNK-S2B CLIN are separate but highly coordinated units which together propose a large, multi-center, randomized controlled trial comparing TNK to rt-PA in patients with acute ischemic stroke treated within 3 hours of onset. The goals of TNK-S2B STAT are: 1) to provide a statistical design which establishes whether, compared to rt-PA, TNK shows promise in reducing poor outcomes following acute ischemic stroke, while minimizing follow-up time and the number of patients required. 2) to conduct, efficiently integrate, and be responsible for all TNK-S2B data management operations. 3) to transmit to the Clinical Coordinating Center (CCC) in a timely fashion all of the data which the principal investigator of TNK-S2B needs to meet his responsibilities in terms of ensuring patient safety and directing all clinical operations. The statistical analysis plan incorporates several innovative features: 1) A sequential selection procedure identifies one of two doses of TNK (0.1 or 0.4 mg/kg) as superior for Major Neurological Improvement at 24 hours. 2) An initial randomized comparison to rt-PA assesses the selected TNK dose for promise or futility. The outcome is the modified Rankin scale at 3 months. 3) If TNK is promising rather than futile, a phase III trial will compare TNK with rt-PA, again with the modified Rankin scale at 3 months as outcome. 3)For efficiency, the 200 patients included in the initial TNK/rt-PA comparison will be included in the phase III trial (overall n = 1908 patients) if it proceeds.