ALIAS II/III Trial:Albumin Therapy in Ischemic Stroke

描述：(申请人提供)。这项计划拨款的目的是提供支持，以开展所需的组织和赠款撰写活动，以准备NIH申请人血清白蛋白(HSAIb)治疗急性缺血性中风神经保护的重大II/III期随机多中心临床试验-ALIAS试验。这一赠款机制使同行能够及早审查拟议试验的理由和设计。请拨资金支持下列活动：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；编制《操作手册》和数据管理计划；开发创新的替代统计设计和分析方法；设计磁共振成像分研究；编制第二阶段/第三阶段别名试验赠款。白蛋白分子的多功能特性使其成为一种独特的神经保护剂，我们的临床前研究表明，对局灶性脑缺血具有一致的高级别神经保护作用。我们由美国国立卫生研究院支持的第一阶段，白蛋白在急性缺血性中风中的剂量递增和安全性试验(NS 40406)，已经确定HSAIB的安全性为1g/kg。静脉注射。在急性缺血性卒中患者中的临床前有效剂量水平，并使我们在实施标准评估措施作为II/III期ALIAS试验的前奏方面获得了经验。ALIAS试验包括单臂II期无效性研究；随后，如果无效性被拒绝，则双臂III期疗效研究。这两项研究都是双盲、安慰剂对照、随机、多中心试验。将对两组受试者进行平行研究：接受tPA治疗的受试者在卒中开始后3小时内接受HSAIb治疗，而非tPA受试者在卒中开始后4.5小时内接受HSAIb治疗。在最小临床效应规模为10%的情况下，无效试验总共需要大约410名患者，而有效性试验需要-1,950名患者。主要的结果衡量标准是3个月后的改良Rankin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.