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

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75万美国人患有有症状的中风，超过1100万人患有无症状的中风。本建议的主要目的是证明，在现场护理人员启动神经保护剂硫酸镁是一种有效和安全的治疗急性中风。该提案是一项多中心、随机、双盲、3期临床试验，采用意向治疗分析，在救护车转运的急性卒中患者中比较硫酸镁与安慰剂。所有入组个体将在卒中发作后2小时内开始研究药物治疗，约一半入组个体将在卒中发作后1小时内开始研究药物治疗。共1298例患者将入组，每个治疗组649例。硫酸镁的剂量为4 g IV负荷剂量，15分钟内给药，随后为16 g IV维持剂量，24小时内给药。主要研究假设是硫酸镁治疗可改善超急性卒中患者的长期功能结局。主要研究终点是卒中后3个月评估的改良兰金量表总体残疾测量值在硫酸镁组和安慰剂组之间的评分分布差异。次要分析将分析神经功能缺损、日常生活活动、总体结局和生活质量指标终点的治疗疗效，以及预先规定的患者亚组，包括缺血性卒中患者、缺血性卒中合并组织纤溶酶原激活剂治疗患者、缺血性卒中未合并组织纤溶酶原激活剂治疗患者、脑出血患者、症状发作15-60分钟内接受治疗的患者，在症状发作后61-120分钟内。该试验的成功实施将作为有前途的神经保护剂硫酸镁在急性卒中中的关键测试，也将首次证明急性卒中患者的现场招募和治疗是3期卒中试验的实用可行策略，允许在超急性时间窗招募更多患者。

Stroke is the third leading cause of death and the leading cause of adult disability in the United States. Each year in the US, 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. 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 1298 patients will be enrolled, 649 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 hyper-acute 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 pre-specified 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 hyper-acute time windows.