Ischemic stroke continues to be a major public health problem, and is the third leading cause of death and the leading cause of disability in adults over age 45 in the United States. To date, no treatment has been proven to be useful in limiting the amount of ischemic brain injury and improving outcome following acute cerebral infarction. Tirilazad mesylate, a 21-aminosteroid lipid peroxidase inhibitor, has shown great promise in reducing infarct size in experimental models of focal brain ischemia and has an excellent record of safety in human trials. The enclosed proposal outlines the details of a large-scale, multi-center, randomized, double-blind, placebo-controlled trial of tirilazad mesylate in patients with symptoms of acute cerebral infarction of less than 6 hours' duration. To expedite the initiation of treatment with study drug as soon as possible after the onset of symptoms, treatment will be initiated before full eligibility is determined, thereby saving valuable minutes during which irreversible changes in brain tissue may be occurring. Fully eligible patients will continue treatment for 72 hours, while all randomized patients will be followed-up at 7-10 days and 3 months. The primary endpoint for the trial will be the proportion of patients (both all randomized and fully eligible) achieving an independent recovery at three months following the stroke. Assuming that 50% of randomized patients may not be fully eligible, we estimate that 2244 patients (1122 in each treatment group) will need to be randomized to detect an absolute improvement rate of 12% in independent recovery in the fully eligible tirilazad group with two tailed alpha=0.05 and power=0.80.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031554-02
Application #
2269480
Study Section
Special Emphasis Panel (SRC (02))
Project Start
1993-08-05
Project End
1996-03-31
Budget Start
1994-06-20
Budget End
1996-03-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Virginia
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Johnston, Karen C; Wagner, Douglas P; Haley Jr, E Clarke et al. (2002) Combined clinical and imaging information as an early stroke outcome measure. Stroke 33:466-72
Johnston, K C; Connors Jr, A F; Wagner, D P et al. (2000) A predictive risk model for outcomes of ischemic stroke. Stroke 31:448-55
Saver, J L; Johnston, K C; Homer, D et al. (1999) Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators. Stroke 30:293-8
Johnston, K C; Li, J Y; Lyden, P D et al. (1998) Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke 29:447-53
(1996) A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). The RANTTAS Investigators. Stroke 27:1453-8