ICH Removal: Minimally Invasive Surgery + rt-PA

描述（由申请人提供）：脑出血（ICH）是唯一一种没有明确治疗方法的卒中。每年有超过10万美国人发生，死亡率为30%至50%，大多数幸存者有严重的运动和认知障碍。少数群体的疾病负担日益加重。损伤的严重程度与血凝块体积和血液暴露于大脑的时间直接相关。没有组织试验来检验血栓清除对ICH卒中患者有益的假设。MISTIE试验是一项概念验证临床试验，具有足够的统计把握度，可对基于图像的微创手术（MIS）抽吸凝块联合术后滴注rt-PA进一步溶解凝块的安全性和临床受益进行明确评价。该试验分为两个步骤：剂量优化，然后是安全性研究。该研究将使用意向治疗分析在7年内完成。最初的目标和假设不变。目前的结果已经提供了关于rt-PA安全性和血凝块溶解、患者选择、患者稳定性、MIS手术有效性定量和治疗相关并发症定义的首次数据。与6例对照受试者相比，在24例受试者中进行了试验手术MIS + rt-PA，死亡率最低，发病率可接受。最初的八个中心中有七个正在有效和热情地执行外科手术和试验程序。在96%的手术中，独立手术中心将手术分级为可接受。该手术导致大多数受试者的血凝块尺寸大幅减小。我们在83%的受试者中清除了50%或更多的凝块（平均清除体积为27 cc），在62.5%的随机化受试者中达到了预定的手术清除目标。最终安全性和结局结果有待招募完成。这些结果将提供MIS对ICH结局影响的稳健估计。这项研究的长期目标是改变ICH的治疗方式，即通过创新和前瞻性的微创手术治疗减少脑损伤。第二类供资提案要求提供290万美元，用于维持审判基础设施，以完成征聘和检验最初的假设。 公共卫生相关性：脑出血（ICH）是唯一没有有效治疗的卒中形式。每年有超过10万美国人发生脑出血。它在30%至50%的所有事件中是致命的，并使大多数幸存者具有显著的运动和认知残疾。少数民族在ICH中承担着越来越多的疾病负担。与缺血性卒中相比，ICH易于快速识别：它发生在年轻患者中，最初对脑组织造成的损伤较小，表明通过正确的治疗（如图像引导微创手术）可以进行干预性改善。然而，在缺血性、动脉瘤破裂和脑内出血等主要卒中亚型中，脑出血是唯一没有明确治疗方法的主要亚型。

DESCRIPTION (provided by applicant): Intracerebral hemorrhage (ICH) is the only form of stroke without a clearly defined treatment. It occurs in more than 100,000 Americans each year, with 30% to 50% mortality and significant motor and cognitive disabilities in the majority of survivors. Minorities bear an increased burden of disease. The severity of the injury is directly related to blood clot volume and time blood is exposed to brain. No trial has been organized to test the hypothesis that blood clot removal benefits the ICH stroke patient. The MISTIE trial is a proof of concept clinical trial with sufficient statistical power to provide a definitive evaluation of the safety and clinical benefit of image-based, minimally invasive surgery (MIS) to aspirate clot in combination with instillations of rt-PA following surgery for further clot dissolution. The trial is in two steps: Dose Optimization followed by a Safety Study. The study will be completed over 7 years, using an intent-to-treat analysis. The original goal and hypotheses are unchanged. The current results have already provided first-time data about rt-PA safety and clot dissolution, patient selection, patient stability, quantitation of MIS surgical effectiveness and definition of treatment related complications. The test surgery, MIS + rt-PA, was performed in 24 subjects with minimal mortality and acceptable morbidity compared to 6 control subjects. Seven of the original eight centers are performing the surgical procedure and the trial procedures effectively and enthusiastically. The surgical procedure has been graded as acceptable by the independent surgical center in 96% of the procedures performed. This surgery has led to substantial reduction of clot size in the majority of subjects. We have removed 50% or more of the clot in 83% of subjects (average volume removed 27 cc) and met the predetermined surgical removal goals in 62.5% of randomized subjects. The final safety and outcome results are pending completion of recruitment. These results will provide robust estimates of effect of MIS on outcome for ICH. The long-term goal of this research is to change the way ICH is treated, that is, to reduce brain injury with innovative and forward-looking minimally invasive surgical management. This type II funding proposal requests $2.9 million to sustain trial infrastructure to complete recruitment and test the original hypothesis. PUBLIC HEALTH RELEVANCE: Intracerebral hemorrhage (ICH) is the only form of stroke without an effective treatment. Intracerebral hemorrhage occurs in over 100,000 Americans each year. It is fatal in 30% to 50% of all occurrences and leaves the majority of the survivors with significant motor and cognitive disability. Minorities bear an increased burden of disease in ICH. Compared to ischemic stroke, ICH is easily and rapidly identified: it occurs in younger patients and initially produces a smaller injury to the cerebral tissues, suggesting that interventional amelioration is possible with the right treatment, such as image- guided, minimally invasive surgery. Yet, of the major stroke subtypes-ischemic, aneurysm rupture, and intracerebral hemorrhage-intracerebral hemorrhage is the only major subtype without a clearly defined treatment.