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亚型。每年有超过10万美国人发生脑出血，幸存者死亡率为30%至50%，并有明显的运动和认知障碍。非洲裔美国人、西班牙裔美国人和亚洲人受到的影响尤为严重。本研究的长期目标是改变脑出血的治疗方式，即通过外科和医疗管理的创新结合来减少脑损伤。该建议是一项II期临床试验，具有足够的统计能力，为基于图像的微创手术（MIS）吸血后安装rt-PA的安全性提供明确的评估。发病率和死亡率与血凝块的体积和血液接触脑组织的时间直接相关。目前还没有组织任何试验来检验清除血凝块是安全的这一假设。我们将提供关于MIS联合rt-PA清除脑出血患者血凝块能力的数据。试验分为两个步骤：剂量发现（连续剂量等级），然后是安全性研究（随机对照试验）。该研究将为选择rt-PA的最佳剂量提供关键信息。研究结果将首次提供有关手术安全性、rt-PA血块溶解和动力学、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。该研究将首次验证血块移除与预后之间的关系，并为成功的III期试验铺平道路，以验证早期和完全移除脑出血可降低发病率和死亡率的总体假设。目的1（第一阶段：剂量发现研究）：对于接受MIS治疗的脑出血患者，我们将评估将rt-PA的每日总剂量从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率。目的2（第1阶段：剂量寻找研究和第2阶段：安全性研究）：我们将测试管内置管和吸入血肿内容物的安全性，然后用低剂量rt-PA冲洗血块。目标是实现几乎完全的凝块溶解，而不会导致手术相关的死亡率、出血或感染率高于接受积极药物治疗的患者的这些事件的发生率。目的3（2期：安全性研究）：我们将评估与传统药物治疗组相比，MIS加溶栓是否能改善手术治疗组的血栓大小溶解。

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.