. 2024 Sep 26;19(9):e0310906.

doi: 10.1371/journal.pone.0310906. eCollection 2024.

Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms

Sakyo Hirai¹, Kyohei Fujita¹, Shoko Fujii¹, Satoru Takahashi¹, Keigo Shigeta², Jun Karakama³, Yukiko Enomoto⁴, Yohei Sato⁵, Masataka Yoshimura^{6

7}, Shin Hirota⁶, Tatsuya Mizoue⁸, Yoshikazu Yoshino⁹, Yoshihisa Kawano^{10

11}, Toshihiro Yamamura¹⁰, Shinya Kohyama⁷, Masaru Hirohata¹², Shinichi Yoshimura¹³, Yosuke Ishii¹⁴, Toshihiro Yamauchi¹⁵, Naoki Taira¹⁶, Yoshiki Obata¹⁷, Makoto Sakamoto¹⁸, Masato Inoue¹⁹, Motoshige Yamashina²⁰, So Tokunaga²¹, Toshio Higashi²², Kana Sawada²³, Hidetoshi Mochida²⁴, Keisuke Ido²⁵, Masataka Takeuchi²⁶, Tomoji Takigawa²⁷, Yasushi Takagi²⁸, Masafumi Morimoto²⁹, Masataka Nanto³⁰, Kazunori Miki³¹, Kouichi Misaki³², Koichi Arimura³³, Yoshiki Hanaoka³⁴, Mutsuya Hara³⁵, Shoko Hara¹¹, Kota Yokoyama³⁶, Jun Ooyama³⁶, Ryoichi Hanazawa³⁷, Hiroyuki Sato³⁷, Akihiro Hirakawa³⁷, Megumi Ishiguro³⁸, Shigeru Nemoto¹⁴, Kazutaka Sumita¹

Affiliations

¹ Department of Endovascular Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Neurosurgery, National Hospital Organization Disaster Medical Center, Tokyo, Japan.
³ Department of Neurosurgery, Ome Medical Center, Tokyo, Japan.
⁴ Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
⁵ Department of Neurosurgery, Japanese Red Cross Musashino Hospital, Tokyo, Japan.
⁶ Department of Neurosurgery, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
⁷ Department of Endovascular Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.
⁸ Department of Neurosurgery, Suiseikai Kajikawa Hospital, Hiroshima, Japan.
⁹ Department of Neuroendovascular Surgery, Jichi Medical University Saitama Medical Center, Saitama, Japan.
¹⁰ Department of Neurosurgery, JA Toride Medical Center, Ibaraki, Japan.
¹¹ Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.
¹² Department of Neurosurgery, Kurume University Hospital, Fukuoka, Japan.
¹³ Department of Neurosurgery, Hyogo Medical University Hospital, Hyogo, Japan.
¹⁴ Department of Neurosurgery, Kanto Rosai Hospital, Kanagawa, Japan.
¹⁵ Department of Neurosurgery, Chiba Emergency and Psychiatric Medical Center, Chiba, Japan.
¹⁶ Department of Neurosurgery, Shuwa General Hospital, Saitama, Japan.
¹⁷ Department of Neurosurgery, Tokyo Kita Medical Center, Tokyo, Japan.
¹⁸ Faculty of Medicine, Department of Brain and Neurosciences, Division of Neurosurgery, Tottori University, Tottori, Japan.
¹⁹ Department of Neurosurgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
²⁰ Department of Neurosurgery, Soka Municipal Hospital, Saitama, Japan.
²¹ Department of Neuroendovascular Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
²² Department of Neurosurgery, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
²³ Department of Neurosurgery, Tokyo Bay Urayasu Ichikawa Medical Center, Chiba, Japan.
²⁴ Department of Neurosurgery, Asahi General Hospital, Chiba, Japan.
²⁵ Department of Neurosurgery, Saga Prefectural Hospital Koseikan, Saga, Japan.
²⁶ Department of Neurosurgery, Seisho Hospital, Kanagawa, Japan.
²⁷ Department of Neurosurgery, Dokkyo Medical University Saitama Medical Center, Saitama, Japan.
²⁸ Department of Neurosurgery, Tokushima University Hospital, Tokushima, Japan.
²⁹ Department of Neurosurgery, Yokohama Shintoshi Neurosurgical Hospital, Kanagawa, Japan.
³⁰ Department of Neurosurgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
³¹ Department of Neuroendovascular Surgery, Tokyo Metropolitan Police Hospital, Tokyo, Japan.
³² Department of Neurosurgery, Kanazawa University Hospital, Kanazawa, Japan.
³³ Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³⁴ Department of Neurosurgery, Shinshu University Hospital, Nagano, Japan.
³⁵ Department of Neurosurgery, Tokyo Metropolitan Toshima Hospital, Tokyo, Japan.
³⁶ Department of Radiology, Tokyo Medical and Dental University, Tokyo, Japan.
³⁷ Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
³⁸ Department of Health Science and Development Center, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 39325746
PMCID: PMC11426478
DOI: 10.1371/journal.pone.0310906

Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms

Sakyo Hirai et al. PLoS One. 2024.

. 2024 Sep 26;19(9):e0310906.

doi: 10.1371/journal.pone.0310906. eCollection 2024.

Authors

Affiliations

¹ Department of Endovascular Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Neurosurgery, National Hospital Organization Disaster Medical Center, Tokyo, Japan.
³ Department of Neurosurgery, Ome Medical Center, Tokyo, Japan.
⁴ Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
⁵ Department of Neurosurgery, Japanese Red Cross Musashino Hospital, Tokyo, Japan.
⁶ Department of Neurosurgery, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
⁷ Department of Endovascular Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.
⁸ Department of Neurosurgery, Suiseikai Kajikawa Hospital, Hiroshima, Japan.
⁹ Department of Neuroendovascular Surgery, Jichi Medical University Saitama Medical Center, Saitama, Japan.
¹⁰ Department of Neurosurgery, JA Toride Medical Center, Ibaraki, Japan.
¹¹ Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.
¹² Department of Neurosurgery, Kurume University Hospital, Fukuoka, Japan.
¹³ Department of Neurosurgery, Hyogo Medical University Hospital, Hyogo, Japan.
¹⁴ Department of Neurosurgery, Kanto Rosai Hospital, Kanagawa, Japan.
¹⁵ Department of Neurosurgery, Chiba Emergency and Psychiatric Medical Center, Chiba, Japan.
¹⁶ Department of Neurosurgery, Shuwa General Hospital, Saitama, Japan.
¹⁷ Department of Neurosurgery, Tokyo Kita Medical Center, Tokyo, Japan.
¹⁸ Faculty of Medicine, Department of Brain and Neurosciences, Division of Neurosurgery, Tottori University, Tottori, Japan.
¹⁹ Department of Neurosurgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
²⁰ Department of Neurosurgery, Soka Municipal Hospital, Saitama, Japan.
²¹ Department of Neuroendovascular Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
²² Department of Neurosurgery, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
²³ Department of Neurosurgery, Tokyo Bay Urayasu Ichikawa Medical Center, Chiba, Japan.
²⁴ Department of Neurosurgery, Asahi General Hospital, Chiba, Japan.
²⁵ Department of Neurosurgery, Saga Prefectural Hospital Koseikan, Saga, Japan.
²⁶ Department of Neurosurgery, Seisho Hospital, Kanagawa, Japan.
²⁷ Department of Neurosurgery, Dokkyo Medical University Saitama Medical Center, Saitama, Japan.
²⁸ Department of Neurosurgery, Tokushima University Hospital, Tokushima, Japan.
²⁹ Department of Neurosurgery, Yokohama Shintoshi Neurosurgical Hospital, Kanagawa, Japan.
³⁰ Department of Neurosurgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
³¹ Department of Neuroendovascular Surgery, Tokyo Metropolitan Police Hospital, Tokyo, Japan.
³² Department of Neurosurgery, Kanazawa University Hospital, Kanazawa, Japan.
³³ Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³⁴ Department of Neurosurgery, Shinshu University Hospital, Nagano, Japan.
³⁵ Department of Neurosurgery, Tokyo Metropolitan Toshima Hospital, Tokyo, Japan.
³⁶ Department of Radiology, Tokyo Medical and Dental University, Tokyo, Japan.
³⁷ Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
³⁸ Department of Health Science and Development Center, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 39325746
PMCID: PMC11426478
DOI: 10.1371/journal.pone.0310906

Erratum in

Correction: Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms.
Hirai S, Fujita K, Fujii S, Takahashi S, Shigeta K, Karakama J, Enomoto Y, Sato Y, Yoshimura M, Hirota S, Mizoue T, Yoshino Y, Kawano Y, Yamamura T, Kohyama S, Hirohata M, Yoshimura S, Ishii Y, Yamauchi T, Taira N, Obata Y, Sakamoto M, Inoue M, Yamashina M, Tokunaga S, Higashi T, Sawada K, Mochida H, Ido K, Takeuchi M, Takigawa T, Takagi Y, Morimoto M, Nanto M, Miki K, Misaki K, Arimura K, Hanaoka Y, Hara M, Hara S, Yokoyama K, Ooyama J, Hanazawa R, Sato H, Hirakawa A, Ishiguro M, Nemoto S, Sumita K. Hirai S, et al. PLoS One. 2025 Aug 4;20(8):e0329657. doi: 10.1371/journal.pone.0329657. eCollection 2025. PLoS One. 2025. PMID: 40758631 Free PMC article.

Abstract

Rationale: Thromboembolism is a serious complication of endovascular treatment for ruptured cerebral aneurysms. The administration of antiplatelet agents before endovascular treatment for ruptured cerebral aneurysms may reduce the risk of thromboembolic complications.

Aim: This study aimed to assess the safety and efficacy of preoperative aspirin administration in endovascular treatment for ruptured cerebral aneurysms.

Sample size estimates: Assuming a 15% incidence rate of both intraoperative thromboembolic morbidity and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans assessed by an Independent Review Committee, a sample size of 484 will be required to detect a 10% improvement with aspirin administration with 90% power using the Pearson's chi-square test at a two-sided significance level of 2.5% for each primary outcome, after accounting for a 5% dropout rate.

Methods and design: ASTOP is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 484 patients with ruptured cerebral aneurysms receiving coil embolization within 72 h of onset will be randomly assigned 1:1 to receive 200 mg of aspirin or placebo before the procedure.

Study outcomes: The primary outcomes will be the incidence rates of intraoperative thromboembolic complications and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans evaluated by the Independent Review Committee. The secondary outcomes will be the incidence rate of cerebral ischemic events and all bleeding events within 14 days of enrollment and functional outcomes defined by the modified Rankin Scale score at 90 days.

Discussion: This trial will provide valuable data on the role of antiplatelet agents during endovascular treatment for ruptured cerebral aneurysms.

Trial registration: Registration: Japan Registry of Clinical Trials, Identifier: jRCTs031210421.

Copyright: © 2024 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

**Fig 1. Study flowchart.**
AEs, adverse events; AG, angiography; CT, computed tomography; MRI, magnetic resonance imaging; mRS, modified Rankin Scale; EVT, endovascular treatment; RAs, ruptured aneurysms.

See this image and copyright information in PMC

References

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Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms

Affiliations

Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances