ALIAS Phase lll Trial Albumin in Acute Ischemic Stroke

ALIAS试验(急性卒中中的白蛋白)是一项随机、双盲、安慰剂对照、多中心、 大剂量人血清白蛋白对急性脑缺血的神经保护作用的III期临床试验 卒中。这项试验建立在大量临床前证据的基础上，即大剂量的白蛋白明显是神经损伤的。 以及我们正在进行的由NIH资助的白蛋白剂量递增和安全性临床试验，该试验已经 完成了六个预先指定的白蛋白剂量等级中的第五个(总共70名受试者)，并表明 更高剂量可以安全地服用，没有白蛋白相关毒性，并强烈建议 功效。值得注意的是，V级剂量(1.71克/公斤)很好地落在每公斤1.25-2.50克/公斤的剂量范围内 在临床前研究中显示具有高度的保护性。ALIAS第三阶段试验的主要目标是 确定与生理盐水安慰剂相比，大剂量白蛋白治疗是否会增加 急性缺血性卒中患者的良好结局。为此，我们建议进行两项 白蛋白治疗慢性支气管炎患者的单独但同时实施的随机双盲试验 基线NIH卒中量表评分(NIHSSS)在6分或以上的急性缺血性卒中，谁可以 卒中后5小时内接受白蛋白治疗。这两项试验将在两个队列中进行：一个是 接受静脉注射的标准护理治疗。TPA；以及没有收到tPA的人。关于以下方面的决定 TPA疗法是基于当地最好的护理标准。主要假设将分别进行检验。 在每个队列中。良好结果被定义为NIHSSS为0或1，或修改后的Rankin分数 (MRS)为0或1，或两者兼而有之，从随机化的3个月测量。审判将包括临时 分析，最多将在美国和加拿大的40个临床地点招募1800名受试者。 ALIAS试验提供了一个独特的机会，可以应用临床前高度有效的策略来治疗 中风使用的剂量和时间与显示疗效的实验环境密切相关。

The ALIAS Trial (Albumin In Acute Stroke) is a randomized, double-blind, placebo-controlled, multicenter, Phase III clinical trial of high-dose human albumin (ALB) therapy for neuroprotection in acute ischemic stroke. The Trial builds upon extensive preclinical evidence that high-dose ALB is markedly neuro- protective; and our ongoing NIH-funded Phase I ALB Dose-Escalation and Safety Clinical Trial, which has completed the fifth of the six pre-specified ALB dose-tiers (total of 70 subjects) and has shown that the higher doses can be safely administered without ALB-related toxicity and with strong suggestions of efficacy. Significantly, dose-tier V (1.71 g/kg) falls well within the per-kg dose-range of 1.25-2.50 g/kg shown in preclinical studies to be highly protective. The primary aim of the ALIAS Phase III Trial is to ascertain whether high-dose ALB therapy, compared to saline-placebo, will increase the proportion of favorable outcome in subjects with acute ischemic stroke. To this end, we propose to conduct two separate but concurrently implemented randomized, double-blinded trials of ALB therapy in patients with acute ischemic stroke whose baseline NIH Stroke Scale Score (NIHSSS) is 6 or greater and who can be treated with ALB within 5 hours of stroke-onset. The two trials will be carried out in two cohorts: one that receives standard-of-care treatment with i.v. tPA; and one that does not receive tPA. Decision regarding tPA therapy is based on the local best standard of care. The primary hypothesis will be tested separately in each cohort. Favorable outcome is defined as either an NIHSSS of 0 or 1, or a modified Rankin Score (mRS) of 0 or 1, or both, measured at 3 months from randomization. The trials will incorporate interim analyses, and a maximum of 1,800 subjects will be recruited at 40 clinical sites in the U.S. and Canada. The ALIAS Trial affords the unique opportunity to apply a preclinically highly effective strategy to treat stroke using a dose and timing that closely replicate the experimental setting in which efficacy was shown.