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Safety and efficacy of indobufen versus aspirin for cerebral small vessel disease: A randomized, double-blind, double-dummy, multicenter (SEIAS) trial protocol

Ying Chen1 ,  Biying Ji1 ,  Yue Cheng1 ,  Qingxiu Zhang1,2 ,  Yun Xu1,2,3,4*
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1 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
2 State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu, China
3 Jiangsu Key Laboratory for Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China
4 Nanjing Neurology Clinical Medical Center, Nanjing, Jiangsu, China
Advanced Neurology, 026140005 https://doi.org/10.36922/AN026140005
Received: 30 March 2026 | Revised: 10 June 2026 | Accepted: 18 June 2026 | Published online: 7 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Indobufen, a reversible multi-target platelet aggregation inhibitor with anticoagulant properties, has been shown to reduce the risk of ischemic cardiovascular and peripheral vascular diseases. However, its efficacy and safety in patients with imaging-confirmed cerebral small vessel disease (CSVD) remain unclear. This trial protocol aims to compare the efficacy and safety of indobufen versus aspirin in patients with imaging-confirmed CSVD. We will conduct a randomized, double-blind, double-dummy, multicenter trial at 16 stroke centers in China. A total of 1,042 eligible patients will be randomly assigned in a 1:1 ratio to receive either indobufen (100 mg twice daily) or aspirin (100 mg once daily) for one year and will be followed for a total of three years. Randomization will be centrally generated by computer and stratified by participating center. The primary endpoint is the occurrence of new lacunar infarctions detected by neuroimaging within one year. Secondary endpoints include other ischemic vascular events (e.g., transient ischemic attack and myocardial infarction), cognitive impairment, and incident dementia. The primary safety outcome is hemorrhagic complications during follow-up.

Keywords
Antiplatelet agents
Cerebral small vessel disease
Lacunar stroke
Randomized controlled trial
Clinical outcomes
Funding
This research was supported by the National Natural Science Foundation of China (82130036), the STI2030-Major Projects (2022ZD0211800), and the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0504902). Additional funding was provided by Jiangsu Province Key Medical Discipline (ZDXK202216).
Conflict of interest
Yun Xu serves as one of the Editors-in-Chief of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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