ICH Removal: Minimally Invasive Surgery + rt-PA

描述（由申请人提供）：脑出血（ICH）是唯一没有明确定义治疗的卒中亚型。ICH每年发生在超过100，000名美国人中，死亡率为30%至50%，幸存者中有严重的运动和认知障碍。非裔美国人、西班牙裔和亚裔受到的影响尤为严重。这项研究的长期目标是改变ICH的治疗方式，即通过手术和药物管理的创新组合来减少脑损伤。该提案是一项II期临床试验，具有足够的统计功效，可对基于图像的微创手术（MIS）抽吸凝块后安装rt-PA的安全性进行明确评价。发病率和死亡率与血凝块的体积和血液暴露于脑组织的持续时间直接相关。没有组织试验来检验血块清除是安全的这一假设。我们将生成关于MIS与rt-PA清除ICH患者血凝块能力的数据。该试验分为两个步骤：剂量探索（连续剂量层），然后是安全性研究（随机对照试验）。该研究将产生对选择rt-PA最佳剂量至关重要的信息。结果将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第一时间数据。这项研究将证明血栓清除与结局之间关系的首次测试，并为成功的III期试验铺平道路，以测试早期和完全清除ICH导致发病率和死亡率降低的总体假设。目标1（第1阶段：剂量探索研究）：对于接受MIS治疗的ICH患者，我们将评价rt-PA的每日总剂量从0.3 mg增加至1.0 mg至3.0 mg是否会增加ICH血凝块溶解速率。目标2（第1阶段：剂量探索研究和第2阶段：安全性研究）：我们将测试植入物内导管放置和抽吸血肿内容物，然后用低剂量rt-PA进行凝块冲洗的安全性。目标是实现几乎完全的血凝块溶解，而手术相关的死亡率、出血或感染发生率不会高于采用积极药物治疗的患者的这些事件发生率。目标3（第二阶段：安全性研究）：我们将评估与常规药物治疗组相比，MIS加溶栓是否改善了手术治疗组的血凝块尺寸溶解。

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.