ICH Removal: Minimally Invasive Surgery + rt-PA

描述(由申请人提供)：脑出血(ICH)是唯一没有明确治疗方法的中风亚型。每年有超过10万名美国人发生ICH，幸存者中有30%到50%的死亡率和严重的运动和认知障碍。非洲裔美国人、西班牙裔和亚洲人受到的影响不成比例。这项研究的长期目标是改变脑出血的治疗方式，即通过手术和医疗管理的创新组合来减少脑损伤。这项建议是一项具有足够统计能力的第二阶段临床试验，以提供对基于图像的微创手术(MIS)的安全性的明确评估，该手术在吸出血栓后安装rt-PA。发病率和死亡率与血凝块的大小和血液接触脑组织的时间直接相关。目前还没有组织试验来检验血栓清除是安全的这一假设。我们将提供有关使用rt-PA的管理信息系统清除脑出血患者血栓的能力的数据。试验分为两个步骤：剂量发现(连续剂量分级)，随后是安全性研究(随机对照试验)。这项研究将提供对选择最佳rt-PA剂量至关重要的信息。研究结果将首次提供有关手术安全性、rt-PA凝块溶解和动力学、患者选择、患者稳定性、治疗相关并发症和手术安全性的数据。这项研究将证明血栓清除和结果之间的关系的第一个测试，并为成功的第三阶段试验铺平道路，以测试早期和完全清除脑出血将降低发病率和死亡率的总体假设。目的1(阶段1：剂量发现研究)：对于接受脑出血治疗的患者，我们将评估将rt-PA总剂量从0.3 mg增加到1.0 mg到3.0 mg是否会增加脑出血血凝块的溶解速度。目的2(阶段1：剂量发现研究和阶段2：安全性研究)：我们将测试腔内置管和血肿内容物抽吸的安全性，然后用小剂量rt-PA进行血块冲洗。其目标是实现几乎完全的血栓溶解，而不会导致与手术相关的死亡率、出血或感染率高于接受积极治疗的患者的这些事件的发生率。目的3(阶段2：安全性研究)：我们将评估在外科治疗组中，与传统内科治疗组相比，微创手术加溶栓是否能改善血栓大小的溶解。

DESCRIPTION (provided by applicant): Intracerebral Hemorrhage (ICH) is the only stroke subtype without a clearly defined treatment. ICH occurs in over 100,000 Americans yearly, with 30% to 50% mortality and significant motor and cognitive disabilities in survivors. African-Americans, Hispanics and Asians are disproportionately affected. The long-term goal of this research is to change the way ICH is treated, that is, to reduce brain injury with an innovative combination of surgical and medical management. This proposal is a Phase II clinical trial with sufficient statistical power to provide a definitive evaluation of the safety of image-based, minimally invasive surgery (MIS) to aspirate clot followed by installations of rt-PA. Morbidity and mortality are directly related to the volume of blood clot and duration of blood exposure to the brain tissue. No trial has been organized to test the hypothesis that blood clot removal is safe. We will produce data regarding the capability of MIS with rt-PA to remove blood clot from ICH patients. The trial is in two steps: Dose Finding (successive dose tiers), followed by a Safety Study (randomized, controlled trial). The study will produce information critical to selecting the optimal dose of rt-PA. The results will provide first-time data about surgical safety, rt-PA clot dissolution and kinetics, patient selection, patient stability, treatment-related complications, and surgical safety. This study would demonstrate the first test of the relation between clot removal and outcome, and prepare the way for a successful Phase III trial to test the overall hypothesis that early and complete removal of ICH results in decreased morbidity and mortality. Aim 1 (Stage 1: Dose-Finding Study): For patients with ICH treated with MIS, we will evaluate if increasing the total daily dose of rt-PA from 0.3 mg to 1.0 mg to 3.0 mg increases the rate of ICH blood clot dissolution. Aim 2 (Stage 1: Dose-Finding Study and Stage 2: Safety Study): We will test the safety of intraclot catheter placement and aspiration of hematoma contents, followed by clot irrigation with low dose rt-PA. The goal is to achieve near total clot dissolution without procedure-related mortality, bleeding or infection rates greater than the rates of these events in patients managed with aggressive medical treatment. Aim 3 (Stage 2: Safety Study): We will assess if MIS plus thrombolysis improves clot size dissolution in the surgical treatment group compared to clot size dissolution in the conventional medical treatment group.