ALIAS Phase IIi Multicenter Clincal Trial -- Albumin in Acute Ischemic Stroke

描述（由申请人提供）：本次竞争性续期申请的目的是完成ALIAS（白蛋白在急性卒中中的应用）多中心临床试验，其目的是确定大剂量人白蛋白治疗（ALB）是否对急性缺血性卒中患者具有神经保护作用。这项由ninds资助的试验正在美国和加拿大约60个临床地点进行，此前有大量临床前研究表明ALB治疗具有高度的神经保护作用；以及一项剂量递增的试点试验，在该试验中，该疗法对中风患者的安全性和耐受性得到了证明，并获得了初步的疗效信号。根据dsm确定的ALIAS多中心试验的前434名受试者的安全性问题，进行了详细的非盲安全性分析，并确定了纳入修订方案的因素（包括年龄上限、强制性液体限制、强制性利尿剂治疗），以提高安全性。ALIAS第二部分试验于2009年2月重新开始，从1100名受试者中招募了280多名受试者。ALIAS第二部分试验是一项随机、双盲、安慰剂对照的III期多中心临床试验，研究对象为急性缺血性卒中患者，这些患者的基线NIHSS评分为bb0.6，并且可以在卒中发作后5小时内接受研究药物治疗。允许标准的溶栓治疗（IV和/或IA tPA和机械凝块溶解）。该试验的主要目的是确定ALB治疗是否在最佳护理标准之上提供神经保护：具体而言，确定与安慰剂治疗相比，ALB治疗是否增加了具有良好结果的受试者比例。良好结局的定义是NIHSS评分为0或1，或修改后的Rankin评分（mRS）为0或1，或两者兼有，在随机分组后3个月测量。研究对象被跟踪了12个月。总共将招募1100名受试者。可以添加选定的欧洲站点。ALIAS试验提供了一个独特的机会，应用临床前高效的策略来治疗缺血性中风，使用的剂量和时间密切复制临床前环境，在其中显示出疗效。

DESCRIPTION (provided by applicant): The objective of this competitive renewal application is to bring to completion the ALIAS (Albumin in Acute Stroke) Multicenter Clinical Trial, whose aim is to ascertain whether high-dose human albumin therapy (ALB) confers neuroprotection in subjects with acute ischemic stroke. This NINDS-funded trial, in progress at around 60 U.S. and Canadian clinical sites, follows upon extensive preclinical studies showing that ALB therapy is highly neuroprotective; and a dose-escalation Pilot Trial, in which the safety and tolerability of this therapy in stroke patients were demonstrated and a preliminary signal of efficacy was obtained. Based on DSMB-identified safety concerns arising in the first 434 subjects of the ALIAS Multicenter Trial, detailed unblinded safety analyses were conducted and factors were identified that were incorporated into a revised protocol (including upper age limit, mandatory fluid restriction, mandatary diuretic therapy) to improve safety. The ALIAS Part 2 Trial then re-commenced in Feb. 2009 and has since enrolled over 280 subjects of the 1,100 required. The ALIAS Part 2 Trial Is a randomized, double-blinded, placebo-controlled Phase III multicenter clinical trial in patients with acute ischemic stroke whose baseline NIHSS score is >6 and who can be treated with study drug within 5 hours of stroke onset. Standard-of-care thrombolytic therapy (IV and/or IA tPA and mechanical clot lysis) Is permitted. The primary aim of the trial is to ascertain whether ALB therapy confers neuroprotection over and above the best standard of care: specifically, to determine whether ALB therapy increases the proportion of subjects with favorable outcome compared to placebo therapy. Favorable outcome is defined as either an NIHSS score of 0 or 1, or a modified Rankin Score (mRS) of 0 or 1, or both, measured at 3 months from randomization. Subjects are followed out to 12 months. A total of 1,100 subjects will be enrolled. Selected European sites may be added. The ALIAS Trial affords the unique opportunity to apply a preclinically highly effective strategy to treat ischemic stroke using a dose and timing that closely replicate the preclinical setting in which efficacy was shown. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and the major cause of chronic disability. There are currently no clinically proven agents to protect the brain from irreversible Injury in stroke. Lab studies have shown that high-dose albumin therapy is strongly protective in stroke models. The ALIAS Multicenter Trial is a randomized, placebo-controlled study to assess whether this therapy improves neurological and functional outcome in ischemic stroke patients. If it does so, it will become a standard of care throughout the world.