HEMORRHAGE EVACUATION EMPLOYING MR ENDOSCOPIC SURGERY TRIAL

描述（由申请人提供）：脑出血是一种毁灭性的致残疾病，30天死亡率估计在35-52%之间，只有20%的幸存者在6个月时独立生存。迄今为止，在随机对照试验中尚未证明手术治疗对脑出血有效，但研究并未侧重于早期和新颖的外科手术。磁共振引导下的内镜手术引流是治疗原发性脑出血的一种很有前途的技术，可以提供微创血肿引流。该项目的A部分提出了一项单中心、随机、对照、盲法结果评估的II期临床试验，在症状出现24小时内MR引导内镜手术疏散与传统医疗管理治疗原发性脑出血的对比，共纳入60例患者，时间超过5年。本提案的中心目的是证明早期磁共振（MR）引导的内窥镜手术疏散对急性脑出血患者是一种可行且潜在有效的治疗方法。潜在疗效的信号将保证关键试验的启动，在该试验中收集的数据将有助于选择终点分析和3期试验的其他方面。在这项试点试验中，主要研究终点将是90天时修改的Rankin全球残疾量表，二分类分析（存活和独立患者的比例）和定量分析。包括扩散灌注成像在内的多模态MRI将用于监测手术治疗和药物治疗的脑出血患者的病理生理变化，以更好地阐明血肿周围损伤的过程及其对治疗的反应。B部分提出了一项遗传分析亚研究，该研究将对内镜下血块清除和血肿周围活检获得的人类脑组织进行分析，以确定血肿周围的分子机制

DESCRIPTION (provided by the applicant): Intracerebral hemorrhage is a devastating and disabling disease, with 30-day mortality rates estimated to be between 35-52%, and only 20% of survivors independent at 6 months. Surgical therapies, to date, have not been demonstrated to be effective for ICH in randomized, controlled trials, but studies have not focused on early and novel surgical procedures. Magnetic resonance-guided endoscopic surgical evacuation is a promising technique for the treatment of primary ICH, providing minimally invasive hematoma evacuation. Part A of this project proposes a single-center, randomized, controlled, blinded outcome evaluation, phase II clinical trial of MR guided endoscopic surgical evacuation vs. conventional medical management for treatment of primary ICH within 24 hrs of symptom onset, in 60 patients over 5 years. The central aim of this proposal is to demonstrate that early magnetic resonance (MR)-guided endoscopic surgical evacuation is a feasible, and potentially efficacious, treatment for patients with acute ICH. A signal of potential efficacy will warrant launch of a pivotal trial, and data gathered in this pilot will aid in selection of the endpoint analysis and additional aspects of a phase 3 trial. In this pilot trial, the primary study endpoint will be the modified Rankin Scale of gIobal disability at 90 days, analyzed dichotomously (proportion of patients alive and independent) and quantitatively. Multi-modal MRI, including diffusion-perfusion imaging, will be employed to monitor the evolving pathophysiologic changes occurring with ICH in both surgically treated and medically managed patients to better elucidate the processes involved in perihematomal injury and their response to therapy. Part B proposes a genetic analysis substudy, in which human brain tissue, obtained from endoscopic clot removal and peri-hematomal biopsy, will be analyzed to identify the molecular mechanisms of peri-hematomal damage. Gene expression patterns will be measured using qualitative, real-time RT-PCR on a hypothesized set of neurotoxic genes, and using cDNA arrays to screen for a larger set of genes important in the evolution of intracranial hemorrhage.