RANDOMIZED TRAIL OF TIRILAZED IN ACUTE STROKE

缺血性中风仍然是一个主要的公共卫生问题， 第三大死亡原因和第一大残疾原因， 美国45岁以上的成年人。 到目前为止，还没有治疗方法。 被证明可用于限制缺血性脑损伤的量， 改善急性脑梗死的预后。 Tirilazad 甲磺酸，一种21-氨基类固醇脂质过氧化物酶抑制剂， 有望减少局灶性脑实验模型中的梗死面积 并且在人体试验中具有良好的安全记录。 的 所附提案概述了一个大规模，多中心， 甲磺酸替拉扎德的随机、双盲、安慰剂对照试验 急性脑梗死症状小于6 小时的持续时间。 加快研究药物治疗的启动 尽快出现症状后，治疗将 在确定完全资格之前启动，从而节省宝贵的 在此期间，脑组织可能发生不可逆的变化。 正在发生。 完全合格的患者将继续治疗72小时， 而所有随机化患者将在7-10天和3天随访， 个月 本试验的主要终点是以下患者的比例： 患者（全部随机化和完全合格）达到 中风后三个月独立恢复。 假设 50%的随机化患者可能不完全合格，我们估计， 2244例患者（每个治疗组1122例）将需要接受随机化 检测到独立恢复的绝对改善率为12%， 完全合格的替拉扎德组，双尾α =0.05， 功率=0.80。

Ischemic stroke continues to be a major public health problem, and is the third leading cause of death and the leading cause of disability in adults over age 45 in the United States. To date, no treatment has been proven to be useful in limiting the amount of ischemic brain injury and improving outcome following acute cerebral infarction. Tirilazad mesylate, a 21-aminosteroid lipid peroxidase inhibitor, has shown great promise in reducing infarct size in experimental models of focal brain ischemia and has an excellent record of safety in human trials. The enclosed proposal outlines the details of a large-scale, multi-center, randomized, double-blind, placebo-controlled trial of tirilazad mesylate in patients with symptoms of acute cerebral infarction of less than 6 hours' duration. To expedite the initiation of treatment with study drug as soon as possible after the onset of symptoms, treatment will be initiated before full eligibility is determined, thereby saving valuable minutes during which irreversible changes in brain tissue may be occurring. Fully eligible patients will continue treatment for 72 hours, while all randomized patients will be followed-up at 7-10 days and 3 months. The primary endpoint for the trial will be the proportion of patients (both all randomized and fully eligible) achieving an independent recovery at three months following the stroke. Assuming that 50% of randomized patients may not be fully eligible, we estimate that 2244 patients (1122 in each treatment group) will need to be randomized to detect an absolute improvement rate of 12% in independent recovery in the fully eligible tirilazad group with two tailed alpha=0.05 and power=0.80.