ALIAS Phase lll Trial Albumin in Acute Ischemic Stroke

ALIAS试验（白蛋白治疗急性卒中）是一项随机、双盲、安慰剂对照、多中心， 大剂量人血白蛋白（ALB）治疗急性缺血性脑损伤神经保护作用的III期临床试验 中风该试验建立在广泛的临床前证据基础上，即高剂量ALB具有显著的神经毒性， 我们正在进行的NIH资助的I期ALB剂量递增和安全性临床试验， 完成了6个预先规定的ALB剂量层中的第5个（共70例受试者），并表明 更高的剂量可以安全地给药，没有ALB相关的毒性， 功效值得注意的是，剂量层V（1.71 g/kg）福尔斯完全落在1.25-2.50 g/kg的每kg剂量范围内 在临床前研究中显示具有高度保护性。ALIAS III期试验的主要目的是 确定与生理盐水-安慰剂相比，高剂量ALB治疗是否会增加 急性缺血性卒中受试者的良好结局。为此，我们建议进行两次 单独但同时实施的ALB治疗患者的随机、双盲试验 基线NIH卒中量表评分（NIHSSS）为6分或更高的急性缺血性卒中， 在中风发作后5小时内用ALB治疗。这两项试验将在两个队列中进行： 接受标准的护理治疗与i. v. tPA;和一个不接受tPA。的决定 tPA治疗基于当地最佳护理标准。将单独检验主要假设 在每个队列中。有利结局定义为NIHSSS评分为0或1分，或改良兰金评分 (mRS)0或1，或两者，在随机化后3个月测量。试验将包括临时 将在美国和加拿大的40个临床研究中心招募最多1，800名受试者。 ALIAS试验提供了一个独特的机会，应用临床前高度有效的治疗策略， 使用与显示有效性的实验设置接近地复制的剂量和时间来治疗中风。

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.