# Oxiracetam and physical activity in preventing cognitive decline after stroke: A multicenter, randomized controlled trial

## TL;DR

A study in South Korea found that oxiracetam did not help prevent cognitive decline after stroke, even when combined with physical activity.

## Contribution

This is the first multicenter trial to evaluate oxiracetam's efficacy in preventing post-stroke cognitive impairment and its interaction with physical activity.

## Key findings

- Oxiracetam showed no significant effect on cognitive outcomes compared to placebo.
- No interaction was found between oxiracetam and physical activity in preventing cognitive decline.
- Exploratory data suggested possible benefits in highly active oxiracetam participants.

## Abstract

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 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.

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.

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.

Graphical abstract