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.
|Effective start/end date||4/1/04 → 3/31/06|
- National Institutes of Health: $204,145.00