Trial design and reporting standards for intraarterial cerebral thrombolysis for acute ischemic stroke.
Trial design and reporting standards for intraarterial cerebral thrombolysis for acute ischemic stroke.
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DOI：
10.1016/s1051-0443(07)60431-x
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发表时间：
2003-08
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影响因子：
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通讯作者：
R. Higashida;A. Furlan;H. Roberts;T. Tomsick;B. Connors;J. Barr;W. Dillon;S. Warach;J. Broderick
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文献类型：
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作者：
R. Higashida;A. Furlan;H. Roberts;T. Tomsick;B. Connors;J. Barr;W. Dillon;S. Warach;J. Broderick
背景和目的——美国国立卫生研究院 (NIH) 估计，中风造成的费用目前每年超过 450 亿美元。中风是北美、欧洲和亚洲第三大死亡原因，也是成人残疾的主要原因之一。文献中现已报道了许多精心设计的随机卒中试验和病例系列，以评估溶栓疗法治疗急性缺血性卒中的安全性和有效性。这些中风试验包括静脉内研究、动脉内研究和两者的组合，以及单独或与溶栓治疗联合使用机械装置去除血栓栓塞和神经保护药物。目前，唯一被证明可以改善急性中风结局的疗法是对引起缺血事件的凝块进行溶栓。中风溶解研究还有改进的空间。不同的标准以及不同的报告标准和定义使得卒中试验之间难以在患者总体结果和治疗效果方面进行直接比较和对比。需要对侧支血流、再通程度、灌注评估和梗死面积等多个变量进行更统一的定义。此外，还有多个未解答的问题需要进一步研究，特别是关于哪些患者最好接受溶栓治疗的问题。临床成功最重要的预测因素之一是治疗时间，静脉组织纤溶酶原激活剂的早期治疗<3小时和动脉内溶栓的早期治疗<6小时，显示出90天临床结果的显着改善和脑出血的减少。改进的成像技术可以识别缺血半暗带并将其与不可逆梗塞组织区分开来，这可能比症状持续时间更准确地选择患者进行治疗。在评估适合溶栓的患者时还存在其他问题。这些包括能够预测特定闭塞部位是否可以成功进行血运重建，预测血运重建后个体患者的预后和结果，特别是预测脑内出血的发展，无论是否有临床恶化。目前尚不清楚通过溶栓治疗实现立即血流恢复是否意味着临床成功和改善的结果。在所有缺血性卒中患者中，再通与观察到的临床获益之间不存在简单的相关性，因为其他交互变量，例如侧支循环、缺血半暗带、病变位置和范围、治疗时间和出血转化，都与结果相互关联。 方法——本文是在美国介入和治疗神经放射学会和介入放射学会技术评估委员会的赞助下撰写的。本文件的目的是为正在进行的急性缺血性脑卒中动脉内脑溶栓试验的研究设计提供指导。它作为北美和欧洲动脉内溶栓试验的背景，讨论了溶栓治疗的局限性，定义了成功的预测因素，并提供了在设计急性卒中动脉内溶栓临床试验期间可能重要的不同考虑因素的基本原理。本指导文件中包括对此类试验的统一报告标准的建议。这些定义和标准主要用于研究试验；然而，他们应该……
Background and Purpose—The National Institutes of Health (NIH) estimates that stroke costs now exceed $45 billion per year. Stroke is the third leading cause of death and one of the leading causes of adult disability in North America, Europe, and Asia. A number of well-designed randomized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke. These stroke trials have included intravenous studies, intra-arterial studies, and combinations of both, as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs, alone or in combination with thrombolytic therapy. At this time, the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event.There is room for improvement in stroke lysis studies. Divergent criteria, with disparate reporting standards and definitions, have made direct comparisons between stroke trials difficult to compare and contrast in terms of overall patient outcomes and efficacy of treatment. There is a need for more uniform definitions of multiple variables such as collateral flow, degree of recanalization, assessment of perfusion, and infarct size.In addition, there are multiple unanswered questions that require further investigation, in particular, questions as to which patients are best treated with thrombolysis. One of the most important predictors of clinical success is time to treatment, with early treatment of <3 hours for intravenous tissue plasminogen activator and <6 hours for intra-arterial thrombolysis demonstrating significant improvement in terms of 90-day clinical outcome and reduced cerebral hemorrhage. It is possible that improved imaging that identifies the ischemic penumbra and distinguishes it from irreversibly infarcted tissue will more accurately select patients for therapy than duration of symptoms. There are additional problems in the assessment of patients eligible for thrombolysis. These include being able to predict whether a particular site of occlusion can be successfully revascularized, predict an individual patient’s prognosis and outcome after revascularization, and in particular, to predict the development of intracerebral hemorrhage, with and without clinical deterioration. It is not clear to assume that achieving immediate flow restoration due to thrombolytic therapy implies clinical success and improved outcome. There is no simple correlation between recanalization and observed clinical benefit in all ischemic stroke patients, because other interactive variables, such as collateral circulation, the ischemic penumbra, lesion location and extent, time to treatment, and hemorrhagic conversion, are all interrelated to outcome.Methods—This article was written under the auspices of the Technology Assessment Committees for both the American Society of Interventional and Therapeutic Neuroradiology and the Society of Interventional Radiology. The purpose of this document is to provide guidance for the ongoing study design of trials of intra-arterial cerebral thrombolysis in acute ischemic stroke. It serves as a background for the intra-arterial thrombolytic trials in North America and Europe, discusses limitations of thrombolytic therapy, defines predictors for success, and offers the rationale for the different considerations that might be important during the design of a clinical trial for intra-arterial thrombolysis in acute stroke. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are mainly intended for research trials; however, they should …