MISTIE III: Cluster Application for the Data Coordinating Center

MISTIE III：数据协调中心集群应用

基本信息

批准号：
8895425
负责人：
Richard Thompson
金额：
$ 73.83万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8895425
关键词：
Address Alteplase American Animal Model Applications Grants Biometry Blood Brain Brain Injuries Catheters Cerebral hemisphere hemorrhage Clinical Clinical Trials Coagulation Process Collaborations Communities Data Data Collection Data Coordinating Center Dose Economics Effectiveness Enrollment Ensure Evaluation Future Goals Grant Growth Health Hematoma Incidence Injury Innovative Therapy Intervention Irrigation Ischemic Stroke Lead Medical Methodology Molecular Monitor National Institute of Neurological Disorders and Stroke Operative Surgical Procedures Outcome Palliative Care Pathway interactions Patients Peer Review Performance Pharmaceutical Preparations Phase Phase III Clinical Trials Prevention program Probability Procedures Protocols documentation Public Health Publications Randomized Recovery Reporting Research Research Design Resource Sharing Role Safety Site Solutions Specific qualifier value Study Subject Surgeon Target Populations Testing Time Tissue Model Training Translating adjudicate aging population base brain tissue clinical application clinically significant cost data management design efficacy testing efficacy trial functional disability functional outcomes improved meetings minimally invasive mortality phase II trial phase III trial post stroke prevent safety testing social symposium trial design

项目摘要

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

描述（由申请人提供）：MISTIE III 独特地解决了脑出血（ICH）患者和研究界的多种未满足的需求。 ICH 每年影响 10 万美国人。它的发病率在上个世纪没有变化，仍然是一个重大的公共卫生问题，只会随着人口老龄化而加剧。预防计划并没有改变脑出血的死亡率或比缺血性中风更严重的长期功能障碍，从而造成灾难性的个人、社会和经济后果。只有 10% 的 ICH 受试者恢复功能独立。旨在预防脑出血生长、脑保护和开放式手术清除的干预措施对这种令人沮丧的结果几乎没有或没有显着影响。与 2005 年和 2012 年 NINDS 的优先事项一致，MISTIE III 将建立在 MISTIE II 的基础上，MISTIE II 是一项 II 期概念验证试验，证实了微创手术溶栓清除的可行性和安全性 (MIS+rt-PA)。 MISTIE II 优化了手术任务，并显示出对减少 ICH 体积的显着效果。突出的结果包括 180 天 (mRS 0-3) 和 365 天 (mRS 0-2)（分别为 11% 和 14%）的良好功能结果的临床重要改善，其体积缩小效果比任何其他策略都更深远正在临床试验中进行测试。这种治疗比任何其他试验都更适用于目前遭受最坏结果的大量病例。这些结果转化为成本降低和患者效用增加，使得这种创新疗法对于进一步研究至关重要。此外，这项二期试验表明，我们简单的培训方案通过基本的外科医生培训可以产生研究质量的手术表现和标准化的减容结果，这些培训将被广泛推广。 MISTIE III 将证实以下中心假设：微创、基于导管的血块尺寸减小与 ICH 患者的长期结果具有临床意义的功能益处相关。从临床和生物学角度来看，MISTIE III 是一条强大的途径，适用于其他多分子策略，可能会进一步减轻对脑组织的损伤。迹象表明，与成熟的组织和动物模型相对应，局部细胞存活率更高，长期恢复得到改善。 MISTIE III 网络可以以严谨的方式实现这些目标，并准备好测试有关 MIS+rtPA 程序的普遍性和有效性的关键假设，以改善 ICH 后的结果。 - MISTIE III：临床协调中心的牵头拨款集群申请