University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Curr Cardiol Rep. 2012 Dec;14(6):761-6. doi: 10.1007/s11886-012-0311-9.
There have been only 3 positive Phase III randomized clinical trials in acute ischemic stroke, all reperfusion therapies (NINDS; PROACT II; ECASS III). The only approved acute stroke therapy is <3-hour IV tPA. Although numerous compounds have shown benefit in animal models of brain infarction, there has never been a positive Phase III randomized clinical trial of a neuroprotectant in acute ischemic stroke. There are many challenges to acute stroke clinical trials but chief among these are the very short therapeutic window ("time is brain") and the issue of stroke heterogeneity. Stroke is a syndrome and only a very small percentage of all stroke patients present to hospitals in time to consider reperfusion therapy. Many drugs have been rushed to trial prematurely based on inadequate preclinical testing. Many trials have been seriously underpowered due to overly optimistic treatment expectations and the risk of brain hemorrhage has precluded aggressive multimodal treatment strategies. Rather than simply relying on a clock, new imaging methods are being developed to identify patients with "tissue at risk" and "salvageable brain" regardless of time of stroke onset. The 7 STAIR conferences have been convened to address these and other challenges to acute ischemic stroke trial design and completion.
仅有 3 项针对急性缺血性脑卒中的阳性 III 期随机临床试验，均为再灌注治疗（NINDS；PROACT II；ECASS III）。唯一批准的急性脑卒中治疗方法是发病后 3 小时内静脉注射 tPA。尽管许多化合物在脑梗死动物模型中显示出益处，但从未有过神经保护剂在急性缺血性脑卒中的 III 期随机临床试验中显示阳性结果。急性脑卒中临床试验面临诸多挑战，但其中最重要的是治疗窗口期极短（“时间就是大脑”）和脑卒中异质性问题。脑卒中是一种综合征，只有极少数脑卒中患者能够及时到医院接受再灌注治疗。许多药物因临床前测试不足而被仓促推向临床试验。由于对治疗效果过于乐观以及脑出血的风险，许多试验的样本量严重不足，从而无法采取积极的多模式治疗策略。新的成像方法正在开发中，以便根据脑卒中发病时间以外的因素来识别“有组织风险”和“可挽救的脑组织”的患者，而不是单纯依靠时间。7 次 STAIR 会议旨在解决急性缺血性脑卒中试验设计和完成方面的这些和其他挑战。
