Targeting Neuroprotection Clinical Trials to Ischemic Stroke Patients With Potential to Benefit From Therapy

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Abstract
Background and Purpose— Clinical trials of neuroprotective drugs have had limited success. We investigated whether selecting patients according to prognostic features would improve the statistical power of a trial to identify an efficacious treatment. Methods— Using placebo data from the Glycine Antagonist in Neuroprotection (GAIN) International and National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA) clinical trials, we developed and validated simple prognostic models for stroke trial end points: Barthel Index ≥95, modified Rankin Scale ≤1, National Institutes of Health Stroke Scale ≤1, and Glasgow Outcome Scale=1. Using these models, we simulated 1000 clinical trials and estimated, under several hypothetical treatment effect patterns of neuroprotection, the effect on statistical power of including only patients with moderate prognosis. We calculated the number of patients that would have to be enrolled to maintain the statistical power achieved ...