HEMORRHAGE EVACUATION EMPLOYING MR ENDOSCOPIC SURGERY TRIAL

描述(由申请人提供)：脑出血是一种破坏性和致残性的疾病，30天的死亡率估计在35-52%之间，6个月后只有20%的幸存者独立。到目前为止，在随机对照试验中，外科治疗还没有被证明对脑出血有效，但研究还没有集中在早期和新的外科手术方法上。磁共振引导下的内窥镜手术清除术是治疗原发性脑出血的一种有前景的技术，提供微创血肿清除术。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，即MR引导的内窥镜手术清除与传统药物治疗相比，在症状出现24小时内对60名患者进行为期5年的治疗。这项建议的中心目的是证明早期磁共振(MR)引导的内窥镜手术清除对于急性脑出血患者是一种可行的、潜在有效的治疗方法。潜在疗效的信号将保证启动一项关键试验，在该试验中收集的数据将有助于选择终点分析和第三阶段试验的其他方面。在这项试点试验中，主要的研究终点将是90天时修改的全球残疾朗金量表，通过二分法(患者存活和独立的比例)和定量分析。包括扩散-灌注成像在内的多模式磁共振成像将被用于监测手术治疗和内科治疗的脑出血患者发生的病理生理变化，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学分析分研究，在该研究中，将分析从内窥镜下血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。 损坏。基因表达模式将使用定性、实时RT-PCR进行测量 在一组假想的神经毒性基因上，并使用cDNA阵列来筛选在颅内出血的进化中重要的一组更大的基因。

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.