Review, historical context, and clarifications of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms.
Review, historical context, and clarifications of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms.
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DOI：
10.1161/strokeaha.113.000878
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发表时间：
2013-09
期刊：
影响因子：
8.3
通讯作者：
NINDS rt-PA Stroke Trial Investigators
中科院分区：
文献类型：
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作者：
Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:;Levine SR;Khatri P;Broderick JP;Grotta JC;Kasner SE;Kim D;Meyer BC;Panagos P;Romano J;Scott P;NINDS rt-PA Stroke Trial Investigators
自1996年FDA批准IV t-PA用于治疗急性缺血性卒中以来，很明显，用于从治疗中排除的几个标准不是基于实际数据，也不是在临床实践中使用的操作定义。在阿替普酶药品说明书中采用NINDS rt-PA卒中研究的所有合格性标准作为禁忌症/警告。许多临床医生表示需要澄清和更好地定义这些治疗标准。一组同时也是卒中医生的研究者共同奋进，为IV t-PA制定更有临床意义和共识驱动的排除标准。这些排除标准中的第一个是“迅速改善中风症状”（RISS）。我们与最初的研究者一起回顾并澄清了历史背景和意图，进行了电子邮件讨论，召开了一次面对面的“RISS峰会”，并广泛获得了经验丰富的卒中医生的理解。从历史上看，NINDS rt-PA卒中试验中该排除标准的目的是避免治疗短暂性脑缺血发作（TIA）-无需治疗即可完全恢复。一致认为，在没有其他禁忌症的情况下，出现任何程度改善但存在潜在致残性持续神经功能缺损的患者应接受IV t-PA治疗。这一说法得到了原始NINDS试验方法的支持，该方法基于与前NINDS试验者的详细讨论和访谈。一致认为仅应监测准备和IV t-PA推注/输注给药所需时间的改善程度。通过协商一致制定了RISS的明确操作定义，以指导未来急性中风的决策。一致认为，应在个体风险和获益以及患者基线功能状态的背景下考虑治疗决策时存在的所有神经功能缺损。通过专家意见和共识，形成了一个结构化的框架和定量方法来定义RISS。RISS这个词应该保留给那些改善到轻度缺陷的人，特别是那些被认为是非残疾的人。建议以此指导今后关于IV t-PA合格性的决策，包括未来研究的设计。对快速改善至非轻度缺陷的患者进行额外研究是不合理的，因为这些患者应该接受治疗。
Since FDA approval of IV t-PA for treatment of acute ischemic stroke in 1996, it has become clear that several criteria used for exclusion from therapy were not based on actual data nor operationally defined for use in clinical practice. All eligibility criteria from the NINDS rt-PA Stroke Study were adopted within the alteplase package insert as contraindications/warnings. Many clinicians have expressed the need for clarification and better definition of these treatment criteria. A group of investigators who also practice as stroke physicians convened a collaborative endeavor to work toward developing more clinically meaningful and consensus-driven exclusion criteria for IV t-PA. The first of these exclusion criteria chosen was “rapidly improving stroke symptoms” (RISS). We reviewed and clarified the historical context and intention with the original investigators, held e-mail discussions, convened an in-person “RISS Summit”, and obtained the understanding of experienced stroke physicians broadly. Historically, the intent of this exclusion criterion within the NINDS rt-PA Stroke Trial was to avoid treatment of transient ischemic attacks (TIAs) – who would have recovered completely without treatment. There was unanimous consensus that, in the absence of other contraindications, patients who experience improvement of any degree, but have a persisting neurological deficit that is potentially disabling, should be treated with IV t-PA. This statement is supported from the methods established for the original NINDS trial, based on detailed discussions and interviews with the former NINDS trialists. It was agreed that improvement should only be monitored for the extent of time needed to prepare and administer the IV t-PA bolus/infusion. An explicit operational definition of RISS was developed by consensus to guide future decision-making in acute stroke. There was unanimous agreement that all neurological deficits present at the time of the treatment decision should be considered in the context of individual risk and benefit as well as the patient’s baseline functional status. A structured framework and quantitative approach towards defining RISS emerged through expert opinion and consensus. The term, RISS, should be reserved for those who improve to a mild deficit, specifically one which is perceived to be nondisabling. This is recommended to guide decision-making regarding IV t-PA eligibility going forward, including the design of future studies. An additional study of patients with rapid improvement to non-mild deficits is not justified as these patients should be treated.