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

TNK-S2 B STAT和TNK-S2 B CLIN是独立但高度协调的单位，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卒中患者中比较TNK和rt-PA。TNK-S2 B STAT的目标是：1）提供一种统计设计，确定与rt-PA相比，TNK是否有望减少急性缺血性卒中后的不良结局，同时最大限度地减少随访时间和所需患者数量。2)进行、有效整合并负责所有TNK-S2 B数据管理操作。3)及时向临床协调中心（CCC）传输TNK-S2 B的主要研究者在确保患者安全和指导所有临床操作方面履行其职责所需的所有数据。统计分析计划包含几个创新功能： 1)序贯选择程序将两种剂量的TNK（0.1或0.4 mg/kg）中的一种鉴定为24小时时主要神经学改善的上级。 2)与rt-PA的初始随机比较评估了所选TNK剂量的有效性或无效性。结果为3个月时的改良兰金量表。 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，再次与修改后的兰金规模在3个月的结果。 3)对于有效性，如果进行III期试验，则初始TNK/rt-PA比较中纳入的200例患者将被纳入III期试验（总计n = 1908例患者）。

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.