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中风形式。每年有超过10万名美国人发生这种疾病，大多数幸存者的死亡率为30%至50%，并出现严重的运动和认知障碍。少数民族承受着更大的疾病负担。损伤的严重程度与血凝块体积和血液暴露到脑中的时间直接相关。还没有组织试验来检验血液凝块清除有益于脑出血卒中患者的假设。Mistie试验是一项概念验证临床试验，具有足够的统计能力，可以对基于图像的微创手术(MIS)抽吸血栓并在手术后滴注rt-PA以进一步溶解血栓的安全性和临床益处提供明确的评估。试验分两步进行：剂量优化，然后进行安全性研究。这项研究将在7年内完成，采用意向治疗分析。最初的目标和假设没有改变。目前的结果已经首次提供了关于rt-PA安全性和血栓溶解、患者选择、患者稳定性、MI手术有效性的量化以及与治疗相关的并发症的定义的数据。与6名对照受试者相比，24名受试者在死亡率最低、发病率可接受的情况下进行了测试手术，即MIS+rt-PA。原来的8个中心中有7个正在有效和热情地执行手术程序和试验程序。在进行的手术中，96%的手术程序被独立外科中心评定为可接受的。这种手术在大多数受试者中导致了血栓大小的显著缩小。在83%的受试者中，我们已经去除了50%或更多的血栓(平均体积去除了27cc)，在62.5%的随机受试者中，我们达到了预定的手术去除目标。最终的安全和结果结果正在等待招募工作的完成。这些结果将为脑出血患者管理信息系统对预后的影响提供可靠的估计。这项研究的长期目标是改变脑出血的治疗方式，即通过创新和前瞻性的微创手术治疗来减少脑损伤。这项第二类供资提案要求提供290万美元，以维持试验基础设施，以完成征聘工作并检验最初的假设。 公共卫生相关性：脑出血(ICH)是唯一一种没有有效治疗的中风形式。每年有超过10万美国人发生脑内出血。在所有发生的病例中，30%到50%是致命的，并使大多数幸存者患有严重的运动和认知障碍。少数民族在非物质文化遗产中承担着更大的疾病负担。与缺血性卒中相比，脑出血易于快速识别：它发生在较年轻的患者中，最初对脑组织造成的损伤较小，这表明通过正确的治疗，如图像引导的微创手术，介入性改善是可能的。然而，在主要的中风亚型中--缺血性、动脉瘤破裂和脑内出血--脑内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.