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75万美国人患有有症状的中风，超过1100万人患有无症状的中风。本提案的中心目的是证明护理人员在该领域使用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。该建议是一项多中心，随机，双盲，3期临床试验，使用意向治疗分析，硫酸镁与安慰剂在救护车运送的急性中风患者中。研究药物将在所有入组患者中风发作两小时内开始使用，大约一半入组患者中风发作一小时内开始使用。总共1270名患者将被纳入研究，每个治疗组635名。硫酸镁的剂量为4克静脉负荷剂量，持续15分钟，随后16克静脉维持剂量，持续24小时。主要的研究假设是硫酸镁治疗可以改善超急性脑卒中患者的长期功能结局。主要研究终点将是硫酸镁组和安慰剂组在卒中后3个月评估的改良Rankin量表全球残疾评分分布的差异。二级分析将分析神经功能缺损、日常生活活动、总体结果和生活质量的终点，以及预先指定的患者亚组的治疗效果，包括缺血性卒中患者、缺血性卒中联合组织型纤溶酶原激活剂、缺血性卒中未联合组织型纤溶酶原激活剂、脑出血患者、症状出现后15-60分钟内治疗的患者和症状出现后61-120分钟内治疗的患者。

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.