ALIAS II/III Trial:Albumin Therapy in Ischemic Stroke

说明：（由申请人提供）。 该计划补助金的目的是提供支持，以开展组织和撰写补助金所需的活动，以准备NIH申请人血清白蛋白（HSAIb）治疗急性缺血性卒中神经保护的主要II/III期随机多中心临床试验-ALIAS试验。 这一拨款机制规定，可对拟议试验的原理和设计进行早期同行审查。 要求提供资金以支持以下活动：确定和征聘研究地点;确定指导委员会成员、独立医疗监测员和中央药房;最后确定方案和病例报告表;制定业务手册和数据管理计划;制定创新的替代药物设计和分析方法;磁共振成像（MRI）子研究的设计;以及II/III期ALIAS试验补助金的准备。 白蛋白分子的多功能特性使其特别适合作为神经保护剂，我们的临床前研究表明，在局灶性脑缺血中具有一致的高级别神经保护作用。 我们的NIH支持的白蛋白治疗急性缺血性卒中的I期、剂量递增和安全性试验（NS 40406）已经确定了HSAIb在1 g/kg剂量下的安全性。kg. i. v.剂量（临床前有效剂量水平），并为我们提供了实施标准评估措施的经验，作为II/III期ALIAS试验的前奏。 ALIAS试验包括一项单组II期无效性研究;随后，如果无效性被拒绝，则进行一项双组III期疗效研究。 两项研究均设计为双盲、安慰剂对照、随机、多中心试验。 将平行研究两个受试者队列：在3小时内接受HSAIb的tPA治疗队列和在4.5小时内接受HSAIb的非tPA队列。中风发作 在最小临床效应量为10%时，无效性试验总共需要约410例患者，有效性试验总共需要约1，950例患者。 主要结局指标是3个月时的改良兰金评分。

DESCRIPTION: (Provided by applicant). The objective of this Planning Grant is to provide support to carry out the organizational and grant-writing activities needed to prepare an NIH application for a major Phase II/III Randomized, Multi-center Clinical Trial of Human Serum Albumin (HSAIb) Therapy for Neuroprotection in Acute Ischemic Stroke - the ALIAS Trial. This grant mechanism provides for early peer review of the rationale and design of the proposed trial. Funding is requested to support the following activities: Identification and recruitment of study sites; identification of Steering Committee members, independent medical monitors, and a central pharmacy; finalization of the protocol and case report forms; development of the Manual of Operations and the Data Management Plan; development of innovative alternative statistical-design and -analysis methods; design of a Magnetic Resonance Imaging (MRI) substudy; and preparation of the Phase II/lll ALIAS Trial grant. The multi-functional properties of the albumin molecule render it uniquely suited as a neuroprotective agent, and our pre-clinical investigations have shown consistent high-grade neuroprotection in focal cerebral ischemia. Our NIH-supported Phase I, dose-escalation and safety trial of albumin in acute ischemic stroke (NS 40406), has established the safety of HSAIb at the1 g./kg. i.v. dose (a pre-clinically efficacious dose level) in patients with acute ischemic stroke, and has given us experience in implementing standard assessment measures as a prelude to the Phase II/III ALIAS Trial. The ALIAS Trial consists of a single-arm Phase II futility study; and subsequently, if futility is rejected, a two-arm Phase III efficacy study. Both studies are designed as double-blind, placebo-controlled, randomized, multi-center trials. Two cohorts of subjects will be studied in parallel: A tPA-treated cohort receiving HSAIb within 3 h, and a non-tPA cohort receiving HSAIb within 4.5 h. of stroke onset. At a minimum clinical effect size of 10%, a total of approximately 410 patients is required for the futility trial, and -1,950 for the efficacy trial. The primary outcome measure is the modified Rankin score at 3 months.