StrokeNet Thrombectomy Endovascular Platform (STEP)

摘要 在美国，中风是导致残疾的第四大原因。大血管闭塞(LVO)亚型是急性缺血性卒中(AIS)中破坏性最大的亚型。最近的关键试验表明，血管内血栓摘除术(EVT)在选定的AIS患者亚群中非常有益。在这些突破性研究之后，迫切需要评估EVT在可能受益的更广泛人群中的益处，并确定这种疗法的局限性，并在正式的临床试验中解决与管理和伴随疗法相关的多个紧迫问题。为了同时高效地回答多个EVT管理问题，南卡罗来纳医科大学的NIH StrokeNet国家数据管理中心(NDMC)与国家协调中心和StrokeNet血栓切除术血管内平台(STEP)执行委员会将在NIH StrokeNet内开发一个强大的EVT临床试验平台。STEP将进行优化，以在总体主协议下明确回答EVT相关问题，提供推理集成框架和共享基础设施，作为随机、多因素、贝叶斯、自适应平台试验。STEP试验团队将开发业务核心和科学咨询小组，旨在支持三大类试验：扩大EVT适应症、创新的EVT设备和伴随的医疗疗法，以及新颖的院前和早期护理技术和系统。基本的STEP主协议将定义最大的一套纳入/排除标准，以允许对所有连续的、有明显的大或中等颅内血管闭塞的AIS患者进行研究。它还将概述总体研究程序和术语，以及统一的统计推理模型。作为一项注册杠杆试验，STEP将通过使用自动传输机制从现有强大、高质量的国家临床注册中心收集数据，将网站的负担降至最低。对不同干预措施的评估将同时或同时在该平台上进行，并将允许共同参加多种干预措施并共享控制措施，以最大限度地提高效率。一组相互排斥的干预措施的详细信息称为域。符合给定域的患者的细节、干预的细节、随机化和适应的规则随后将在STEP MASTER方案的特定域附录中详细说明。STEP试验的主要终点是在90天时有利的全球残疾水平，使用修正的兰金量表(MRS)的效用加权分析进行评估。STEP试验将允许对治疗策略进行最有效的测试，并允许快速优化血管内治疗环境和急性中风护理。

ABSTRACT Stroke is the fourth leading cause of disability within the United States. Large vessel occlusion (LVO) subtype of acute ischemic stroke (AIS) is the most devastating among all. Recent pivotal trials demonstrated endovascular thrombectomy (EVT) to be highly beneficial in selected subsets of AIS patients. In the wake of these breakthrough studies, an urgent need exists to assess the benefit of EVT in broader populations that are likely to benefit and determine the limits of this therapy, and to address multiple pressing related issues of management and concomitant therapies, in formal clinical trials. To answer multiple EVT management questions efficiently and concurrently, the NIH StrokeNet National Data Management Center (NDMC) at the Medical University of South Carolina, along with the National Coordinating Center and StrokeNet Thrombectomy Endovascular Platform (STEP) Executive Committee, will develop a robust EVT clinical trial platform within NIH StrokeNet. STEP will be optimized to definitely answer EVT-related questions under an overarching Master Protocol, providing an inferentially integrated framework and shared infrastructure, as a randomized, multi-factorial, Bayesian, adaptive platform trial. The STEP trial team will develop operational cores and scientific advisory groups designed to support three broad categories of trials: expansion of EVT indications, innovative EVT devices and concomitant medical therapies, and novel pre- and early-hospital technologies and systems of care. The foundational STEP Master Protocol will define the largest set of inclusion/exclusion criteria to allow study of all consecutive AIS patients with a visible large or medium intracranial vessel occlusion. It also will outline overall study procedures and terminologies, and the unifying statistical inferential model. As a registry-leveraged trial, STEP will minimize burden on the sites by collecting data using an automated transfer mechanism from existing robust, high-quality national clinical registries. Assessment of distinct interventions will be feasible on the platform concurrently or in tandem, and co-enrollment in multiple interventions and sharing of controls will be allowed to maximize efficiency. Details of a mutually exclusive set of interventions are called Domains. The details of patients eligible for a given domain, details of intervention, rules for randomization and adaptation would subsequently be detailed in domain-specific Appendices to the STEP master protocol. The primary endpoint of the STEP trial is favorable global disability level at 90 days, assessed using utility-weighted analysis of the modified Rankin scale (mRS). The STEP trial will allow most efficient testing of treatment strategies and allow rapid optimization of endovascular treatment landscape and acute stroke care.