ALIAS II/III Trial:Albumin Therapy in Ischemic Stroke

ALIAS II/III 试验：白蛋白治疗缺血性中风

• 批准号: 6796049
• 负责人: MYRON DAVID GINSBERG
• 金额: $ 20.41万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6796049
• 关键词: albumins; cardiovascular disorder chemotherapy; cerebral ischemia /hypoxia; clinical trial phase II; clinical trial phase III; dosage; neurology; neuroprotectants; stroke; stroke therapy

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.

描述：（由申请人提供）。 该规划拨款的目的是为开展组织和拨款写作活动提供支持，以准备 NIH 申请，用于急性缺血性中风神经保护的人血清白蛋白 (HSAIb) 疗法的主要 II/III 期随机、多中心临床试验 - ALIAS 试验。 这种资助机制为拟议试验的理由和设计提供了早期同行评审。 请求资金支持以下活动： 确定和招募研究地点；确定指导委员会成员、独立医疗监察员和中央药房；方案和病例报告表的定稿；制定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；磁共振成像 (MRI) 子研究的设计；并准备 II/III 期 ALIAS 试验补助金。 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，其对局灶性脑缺血具有一致的高级神经保护作用。 我们由 NIH 支持的白蛋白治疗急性缺血性中风的 I 期剂量递增和安全性试验 (NS 40406) 已确定 HSAIb 在 1 g/kg 时的安全性。静脉注射急性缺血性中风患者的剂量（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 试验包括单臂 II 期无效研究；随后，如果无效性被拒绝，则进行双组 III 期疗效研究。 这两项研究均设计为双盲、安慰剂对照、随机、多中心试验。 将并行研究两组受试者：tPA 治疗组在 3 小时内接受 HSAIb，非 tPA 治疗组在 4.5 小时内接受 HSAIb。中风发作。 在最小临床效应大小为 10% 时，无效性试验总共需要大约 410 名患者，有效性试验需要 -1,950 名患者。 主要结果指标是 3 个月时的改良 Rankin 评分。