Abstract
INTRODUCTION: This multicenter, double-blind, placebo-controlled trial, commissioned by South Korea's Ministry of Food and Drug Safety, evaluated the effect of oxiracetam for preventing post-stroke cognitive impairment (PSCI) and explored potential interaction with physical activity using neuroimaging. PATIENTS AND METHODS: Patients at high risk of PSCI, reporting subjective cognitive decline ⩾3 months after stroke, were randomized 1:1 to receive oxiracetam or placebo for 36 weeks. Physical activity was tracked via wrist-worn actigraphy. Coprimary endpoints were changes in Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB). Secondary outcomes included neuropsychological assessments and resting-state functional magnetic resonance imaging network metrics. RESULTS: Of 500 enrolled participants (mean age 68.9 years; median 32 months post-stroke), 457 completed the study. There were no statistically significant differences between groups in changes in MMSE (oxiracetam: +0.13 ± 2.27 vs placebo: +0.27 ± 2.09; p = 0.49) or CDR-SB scores (-0.14 ± 0.70 vs -0.08 ± 0.80; p = 0.38). No evidence of interaction was observed between oxiracetam and physical activity. Exploratory analyses suggested favorable trends in functional segregation and CDR-SB scores among highly active oxiracetam participants. DISCUSSION AND CONCLUSION: Oxiracetam did not demonstrate benefit in preventing PSCI in high-risk patients. These findings support the recent regulatory decision to suspend its use in South Korea.