Field Administration of Stroke Therapy-Magnesium Trial (FAST-MAG)

描述(申请人提供)：中风是美国第三大致死原因，也是导致成人残疾的首要原因。在美国，每年有79.5万美国人患有症状性中风。这项建议的中心目的是证明辅助医疗启动的神经保护剂硫酸镁是一种有效和安全的急性中风治疗方法。该提案是一项多中心、随机、双盲、3期临床试验，使用意向治疗分析，在救护车运送的急性中风患者中使用硫酸镁与安慰剂。研究试剂将在所有受试者中风发作后两小时内开始使用，在大约一半受试者发病后一小时内开始使用。总共将有1700名患者入选，每个治疗组850人。所使用的硫酸镁剂量将是15分钟内4克静脉注射负荷量，然后是24小时内16克静脉注射维持量。主要的研究假设是，硫酸镁治疗可以改善超急性中风患者的长期功能结果。主要的研究终点将是硫酸镁组和安慰剂组在中风后3个月评估的全球残疾的改良兰金量表上得分分布的差异。二次分析将分析指标神经功能缺陷、日常生活能力、全球结局和生活质量的终点的治疗效果，以及预先指定的患者亚组中的治疗效果，包括缺血性中风、联合使用组织纤溶酶原激活剂治疗的缺血性中风患者、未联合使用组织纤溶酶原激活剂治疗的缺血性中风患者、脑出血患者、在症状出现15-60分钟内和症状出现61-120分钟内接受治疗的患者。这项试验的成功进行将成为对前景看好的神经保护剂硫酸镁在急性中风中的关键测试，还将首次证明，急性中风患者的现场登记和治疗是第三阶段中风试验的实用和可行的战略，允许在超急性时间窗口登记更多的患者。 公共卫生相关性：在美国，中风是第三大死亡原因，也是导致成人残疾的主要原因。这项招募了1700名患者的临床试验的中心目标是证明现场辅助医疗开始使用脑保护剂硫酸镁可以改善中风结果。这项试验的成功进行将成为对前景看好的神经保护剂硫酸镁在急性中风中的关键测试，还将首次证明，对急性中风患者进行现场治疗是中风试验的一种实用策略，允许更多的患者在发病后两小时内进入危急状态。

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death and the leading cause of adult disability in the United States. Each year in the US, 795,000 Americans suffer a symptomatic stroke. The central aim of this proposal is to demonstrate that paramedic initiation of the neuroprotective agent magnesium sulfate in the field is an efficacious and safe treatment for acute stroke. The proposal is a multicenter, randomized, double-blind, phase 3 clinical trial, using intention to treat analysis, of magnesium sulfate versus placebo among ambulance-transported patients with acute stroke. Study agent will be initiated within two hours of stroke onset in all enrolled individuals, and within one hour of onset in approximately one- half of enrolled individuals. A total of 1700 patients will be enrolled, 850 in each treatment arm. The dose of magnesium sulfate employed will be 4 gram IV loading dose over 15 minutes followed by 16 gram IV maintenance dose over 24 hours. The primary study hypothesis is that treatment with magnesium sulfate improves the long-term functional outcome of hyperacute stroke patients. The primary study endpoint will be the difference in distribution of scores between magnesium sulfate and placebo groups on the modified Rankin Scale measure of global handicap, assessed 3 months poststroke. Secondary analyses will analyze treatment efficacy on endpoints indexing neurologic deficit, activities of daily living, global outcome, and quality of life, and in prespecified patient subgroups, including patients with ischemic stroke, ischemic stroke co-treated with tissue plasminogen activator, ischemic stroke not co-treated with tissue plasminogen activator, intracerebral hemorrhage, patients treated within 15-60 minutes of symptom onset, and within 61-120 minutes of symptom onset. Successful conduct of the trial will serve as a pivotal test of the promising neuroprotective agent magnesium sulfate in acute stroke, and will also demonstrate for the first time that field enrollment and treatment of acute stroke patients is a practical and feasible strategy for phase 3 stroke trials, permitting enrollment of greater numbers of patients in hyperacute time windows. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and the leading cause of adult disability in the United States. The central aim of this clinical trial enrolling 1700 patients is to demonstrate that paramedic start of the brain protective agent magnesium sulfate in the field improves stroke outcomes. Successful conduct of the trial will serve as a pivotal test of the promising neuroprotective agent magnesium sulfate in acute stroke, and will also demonstrate for the first time that field treatment of acute stroke patients is a practical strategy for stroke trials, permitting enrollment of greater numbers of patients in the critical first two hours early after onset.