HEMORRHAGE EVACUATION EMPLOYING MR ENDOSCOPIC SURGERY TRIAL

描述（由申请人提供）：脑出血是一种毁灭性和致残性疾病，30天死亡率估计在35- 52%之间，6个月时只有20%的幸存者独立。迄今为止，在随机对照试验中尚未证明手术治疗对ICH有效，但研究并未集中于早期和新型手术。磁共振引导下的内窥镜手术清除是治疗原发性ICH的一种有前途的技术，可提供微创血肿清除。该项目的A部分提出了一项单中心、随机、对照、盲态结局评价、II期临床试验，在60例患者中比较MR引导内镜下手术清除与传统药物治疗在症状发作24小时内治疗原发性ICH的效果，时间超过5年。本提案的主要目的是证明早期磁共振（MR）引导的内镜手术清除是急性ICH患者的可行且潜在有效的治疗方法。潜在疗效的信号将保证启动关键试验，在该试点中收集的数据将有助于选择终点分析和III期试验的其他方面。在这项初步试验中，主要研究终点将是90天时改良的兰金全球残疾量表，进行二分分析（存活和独立的患者比例）和定量分析。将采用多模式MRI（包括弥散灌注成像）监测手术治疗和药物治疗患者ICH的病理生理学变化，以更好地阐明血肿周围损伤及其对治疗的反应。B部分提出了一项遗传分析子研究，其中将分析从内窥镜凝块清除和血肿周围活检获得的人脑组织，以确定血肿周围的分子机制。 损害将使用定性实时RT-PCR测量基因表达模式 对一组假设的神经毒性基因，并使用cDNA阵列筛选更大的一组基因在颅内出血的演变重要。

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.