MISTIE III: Cluster Application for the Data Coordinating Center

描述(由申请人提供)：Mistie III独一无二地解决了脑出血(ICH)患者和研究社区的多种未得到满足的需求。ICH每年影响10万美国人。它的发病率在上个世纪没有变化，它仍然是一个重大的公共卫生问题，只会随着我们的人口老龄化而加剧。预防计划并未改变脑出血死亡率或大于缺血性中风的长期功能损害，从而造成灾难性的个人、社会和经济后果。只有10%的脑出血受试者恢复到功能独立。旨在防止脑出血增长、脑保护和开放手术后送的干预措施对这一令人沮丧的结果几乎或没有显著影响。与2005和2012年NINDS的优先事项一致，Mistie III将以Mistie II为基础，这是一项第二阶段概念验证试验，证实了溶栓凝块清除的微创手术的可行性和安全性 (mis+rt-PA)。Mistie II优化了手术任务，并在减少脑出血体积方面表现出显著的效果。突出的结果包括180天(MRS 0-3)和365天(MRS 0-2)良好功能结果的临床重要改善(分别为11%和14%)，其容量减少效果比临床试验中测试的任何其他策略都更深刻。与任何其他试验相比，这种治疗方法特别适用于目前遭受最严重后果的较大数量的病例。这些结果转化为降低成本和增加患者效用，使这一创新疗法对进一步研究至关重要。此外，这项第二阶段的试验表明，我们的SIMPLE培训方案产生了研究质量的手术效果和标准化的减容结果，而基本的外科医生培训将广泛推广。MISTIE III将证实中心假设，即微创的、基于导管的血栓大小缩小与临床上对脑出血患者的长期结果有显著的功能益处有关。在临床和生物学上，Mistie III是一种强大的途径，适用于其他可能进一步减轻脑组织损伤的多分子策略。迹象表明，与建立良好的组织和动物模型相对应，局部细胞存活率更高，长期恢复更好。Mistie III网络可以严谨地实现这些目标，并准备检验有关管理信息系统+rtPA程序的普适性和有效性的关键假设，以改善脑出血后的结果。-Mistie III：临床协调中心的牵头赠款-集群申请

DESCRIPTION (provided by applicant): MISTIE III uniquely addresses the multiple unmet needs of both patients with intracerebral hemorrhage (ICH) and the research community. ICH impacts 100,000 Americans each year. Its incidence has remained unchanged over the last century and it remains a substantial public health problem that will only grow with our aging population. Prevention programs have not changed the ICH mortality rate or the long-term functional impairment that is greater than in ischemic stroke, with disastrous personal, social and economic consequences. Only 10% of ICH subjects return to functional independence. Interventions aimed at preventing ICH growth, brain protection, and open surgical evacuation has shown little or no significant impact on this dismal outcome. Consistent with the 2005 & 2012 NINDS priorities, MISTIE III will build on MISTIE II, a Phase II proof-of-concept trial that confirmed the feasibility and safety of minimally invasive surgery for thrombolytic clot evacuation (MIS+rt-PA). MISTIE II optimized the surgical task and demonstrated a dramatic effect on ICH volume reduction. Highlighted results include clinically important improvement in good functional outcomes at both 180 days (mRS 0-3) and 365 days (mRS 0-2) (11% & 14%, respectively), with a volume reduction effect more profound than any other strategies being tested in clinical trials. This treatment, more than any other trial, specifically applies to a larger volume of cases who currently suffer the worst outcomes. These results translate into decreased cost and increased patient utility, making this innovative therapy critically important to further investigate. Additionally, this Phase II trial demonstrated that our simple training protocol produced investigational-quality surgical performance and standardized volume-reduction results with basic surgeon training that will be widely generalizable. MISTIE III will confirm the central hypothesis that minimally invasive, catheter-based clot-size reduction is associated with clinically significant functional benefits in the long-term outcome of the ICH patient. Clinically and biologically, MISTIE III is a robust pathway applicable to other multiple molecular strategies that might further mitigate injury to brain tissue. Indications point to greater local cellular surival and improved long-term recovery corresponding to the well-established tissue and animal models. The MISTIE III network can accomplish these goals with demonstrated rigor and is ready to test the critical hypotheses regarding the generalizability and effectiveness of the MIS+rtPA procedure to improve outcome after ICH. - MISTIE III: Lead Grant-Cluster Application for the Clinical Coordinating Center