Field Administration of Stroke Therapy - Magnesium Trial

描述(由申请人提供)：中风是美国第三大死亡原因和成人残疾的主要原因。在美国，每年有75万美国人患有症状性中风，超过1100万人患有无症状中风。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启动，并在大约一半受试者发病后一小时内启动。总共将招募1270名患者，每个治疗组635名。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、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3期中风试验的一种实用和可行的战略，允许在超急性时间窗口登记更多的患者。

DESCRIPTION (provided by the applicant): Stroke is the third leading cause of death and the leading cause of adult disability in the United States. Each year in the U.S., 750,000 Americans suffer a symptomatic stroke, and over 11 million suffer an asymptomatic 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. A 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 1,270 patients will be enrolled, 635 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 post-stroke. 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.