Optimal Duration of Dual Antiplatelet Therapy After Stent-assisted Coiling

Optimal Duration of Dual Antiplatelet Therapy After Stent-assisted Coiling of Unruptured Intracranial Aneurysms: A Prospective Randomized Multicenter Trial

Comparison of duration of dual antiplatelet therapy after stent-assisted coiling of unruptured intracranial aneurysms

Study Overview

• Status: Completed
• Conditions: Endovascular Procedures; Aneurysm Cerebral
• Intervention / Treatment: Drug: Aspirin 100mg; Drug: Clopidogrel 75mg

Detailed Description

The purpose of this study is to compare the incidence of thromboembolic and hemorrhagic complications between 1 and 18 months after stent-assisted coiling according to the duration of use of dual antiplatelet agents (6 months versus 12 months) after stent-assisted coiling of unruptured intracranial aneurysms to determine the optimal duration of use of dual antiplatelet agents.

• Study Type: Interventional
• Enrollment (Actual): 528
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Korea
  • Daegu, South Korea, 42601
    • Keimyung University Dongsan Medical Center
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 04401
    • Soonchunhyang University Seoul Hospital
  • Seoul, South Korea, 06273
    • Yonsei University Gangnam Severance Hospital
  • Uijeongbu-si, South Korea, 11765
    • Uijeongbu St. Mary's Hospital
  • Chungcheongnam-do
    • Sejong, Chungcheongnam-do, South Korea, 30099
      • Chungnam National University Sejong Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University Yangsan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• subjects over 19 years old
• subjects with modified Rankin Scale (mRS) ≤ 2
• subjects with unruptured intracranial aneurysms

• subjects with appropriated aspirin and clopidogrel reaction units after dual antiplatelet preparation (100 mg of aspirin and 75 mg of clopidogrel) for at least 5 days before procedure [measured using VerifyNow]

  1. aspirin reaction unit (ARU) < 550
  2. P2Y12 reaction unit (PRU): 85~219
• subjects who agreed to this study (with informed consent)

Exclusion Criteria:

• subjects with neurological deficits (mRS ≥ 3)
• subjects with an allergic reaction to antiplatelets (aspirin and clopidogrel) or contrast
• subjects with a high risk of hemorrhage such ICH or severe gastric ulceration
• subjects with coagulopathy
• subjects with thrombocytopenia (<100,000/mm3)
• subjects with liver diseases (> 100IU/L of aspartate aminotransferase or alanine aminotransferase)
• subjects with renal diseases (> 2mg/dL of serum creatinine)
• subjects with underlying diseases that need to maintain dual antiplatelet drugs or anticoagulants.
• subjects with a high risk of strokes (atrial fibrillation, over 70% cerebral artery stenosis or cerebral artery occlusion, moyamoya disease, vascular malformations, etc)
• subjects with uncontrolled congestive heart failure or angina
• subjects with malignant tumors
• subjects with a positive pregnancy test (serum or urine)
• subjects who are unconscious at the time of diagnosis.
• subjects who are unable to complete the required follow-ups
• subjects with life-threatening diseases
• subjects with medical conditions with a life expectancy of less than two years
• subjects who are determined to be disqualified by researchers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: short-term dual antiplatelet group; Patients with unruptured intracranial aneurysms received dual antiplatelet agents (100mg of aspirin and 75mg of clopidogrel) for at least five days before coil embolization. One day prior to coiling, aspirin reaction units (ARU) and P2Y12 reaction units (PRU) were measured using VerifyNow. Patients with proper aspirin and clopidogrel reaction units (ARU < 550 and PRU 85 ~219) will be enrolled in this study. After stent-assisted coiling, dual antiplatelet treatment continued for 6 months; after that time, this therapy will be exchanged for daily oral 100mg of aspirin for 18 months after coiling	Drug: Aspirin 100mg; short-term dual antiplatelet: dual antiplatelet agents for 6 months; long-term dual antiplatelet: dual antiplatelet agents for 12 months; Other Names: Aspirin protect; Aspirin enteric coated; Drug: Clopidogrel 75mg; short-term dual antiplatelet: dual antiplatelet agents for 6 months; long-term dual antiplatelet: dual antiplatelet agents for 12 months; Other Names: Plavix; Plavitor; Celavix; Pregrel; Cloart; Platless; Pidogle; Antipla; Jgrel
Experimental: long-term dual antiplatelet group; Patients with unruptured intracranial aneurysms received dual antiplatelet agents (100mg of aspirin and 75mg of clopidogrel) for at least five days before coil embolization. One day prior to coiling, aspirin reaction units (ARU) and P2Y12 reaction units (PRU) were measured using VerifyNow. Patients with proper aspirin and clopidogrel reaction units (ARU < 550 and PRU 85 ~219) will be enrolled in this study. After stent-assisted coiling, dual antiplatelet treatment continued for 12 months; after that time, this therapy will be exchanged for daily oral 100mg of aspirin for 18 months after coiling.	Drug: Aspirin 100mg; short-term dual antiplatelet: dual antiplatelet agents for 6 months; long-term dual antiplatelet: dual antiplatelet agents for 12 months; Other Names: Aspirin protect; Aspirin enteric coated; Drug: Clopidogrel 75mg; short-term dual antiplatelet: dual antiplatelet agents for 6 months; long-term dual antiplatelet: dual antiplatelet agents for 12 months; Other Names: Plavix; Plavitor; Celavix; Pregrel; Cloart; Platless; Pidogle; Antipla; Jgrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of thromboembolic complications	The primary outcome measure is incidence of thromboembolic complications between 1 and 18 months post-procedure.	between 1 and 18 months after stent-assisted coil embolization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of periprocedural complications	Incidence of periprocedural complications during procedure and within 1 month post-procedure	during procedure and within 1 month post-procedure
Incidence of hemorrhagic complications	Incidence of hemorrhagic complications between 1 and 18 months post-procedure.	between 1 and 18 months after stent-assisted coil embolization
Changes of modified Rankin scale in clinical and functional outcomes at 18 months follow up	Changes in clinical and functional outcomes at 18 months follow up, as measured by an increase in the modified Rankin Scale compared to baseline (modified Rankin Scale: 0) no symptoms, 1) able to carry out all usual activities, despite some symptoms, 2) able to look after own affairs without assistance, but unable to carry out all previous activities, 3) requires some help, but able to wal unassisted, 4) unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5) requires constant nursing care and attention, bedridden, incontinent and 6) dead.	within 18 months post-procedure
Incidence of unrelated complication with this study	Incidence of myocardial infarction and unrelated thromboembolic or hemorrhagic complications with this study	within 18 months post-procedure
Changes in aspirin reaction unit and P2Y12 reaction units at 6 months follow-up by using VerifyNow	Change in aspirin reaction unit and P2Y12 reaction unit at the time of 6 months follow-up compared to baseline by using VerifyNow (Accumetrics, USA)	at 6 months
Periprocedural mortality	Death within 1 month	within 1 month
Comparison of mortality	Death between 1 and 18 months post-procedure	between 1 and 18 months after stent-assisted coil embolization
Changes in radiological outcomes by Roy-Raymond grades	Change in radiological outcomes at 18 months follow up compared to baseline as measured by Roy-Raymond grades: 1) complete, 2) residual neck, and 3) residual sac	at 18 months

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Gangnam Severance Hospital, Yonsei University College of Medicine; Asan Medical Center; Keimyung University Dongsan Medical Center; Soonchunhyang University Hospital; Pusan National University Yangsan Hospital; Chungnam National University Sejong Hospital; Uijeongbu St. Mary's Hospital
• Investigators: Principal Investigator: O-Ki Kwon, Seoul National University Bundang Hospital

Publications and helpful links

General Publications

• Hwang G, Kim JG, Song KS, Lee YJ, Villavicencio JB, Suroto NS, Park NM, Park SJ, Jeong EA, Kwon OK. Delayed ischemic stroke after stent-assisted coil placement in cerebral aneurysm: characteristics and optimal duration of preventative dual antiplatelet therapy. Radiology. 2014 Oct;273(1):194-201. doi: 10.1148/radiol.14140070. Epub 2014 Jun 11.
• Hwang G, Huh W, Lee JS, Villavicencio JB, Villamor RB Jr, Ahn SY, Kim J, Chang JY, Park SJ, Park NM, Jeong EA, Kwon OK. Standard vs Modified Antiplatelet Preparation for Preventing Thromboembolic Events in Patients With High On-Treatment Platelet Reactivity Undergoing Coil Embolization for an Unruptured Intracranial Aneurysm: A Randomized Clinical Trial. JAMA Neurol. 2015 Jul;72(7):764-72. doi: 10.1001/jamaneurol.2015.0654.
• Kim CH, Hwang G, Kwon OK, Ban SP, Chinh ND, Tjahjadi M, Oh CW, Bang JS, Kim T. P2Y12 Reaction Units Threshold for Implementing Modified Antiplatelet Preparation in Coil Embolization of Unruptured Aneurysms: A Prospective Validation Study. Radiology. 2017 Feb;282(2):542-551. doi: 10.1148/radiol.2016160542. Epub 2016 Sep 2.
• Kim T, Kim CH, Kang SH, Ban SP, Kwon OK. Relevance of Antiplatelet Therapy Duration After Stent-Assisted Coil Embolization for Unruptured Intracranial Aneurysms. World Neurosurg. 2018 Aug;116:e699-e708. doi: 10.1016/j.wneu.2018.05.071. Epub 2018 May 17.
• Hwang G, Jung C, Park SQ, Kang HS, Lee SH, Oh CW, Chung YS, Han MH, Kwon OK. Thromboembolic complications of elective coil embolization of unruptured aneurysms: the effect of oral antiplatelet preparation on periprocedural thromboembolic complication. Neurosurgery. 2010 Sep;67(3):743-8; discussion 748. doi: 10.1227/01.NEU.0000374770.09140.FB.
• Almekhlafi MA, Al Sultan AS, Kuczynski AM, Brinjikji W, Menon BK, Hill MD, Goyal M. Antiplatelet therapy for prevention of thromboembolic complications in coiling-only procedures for unruptured brain aneurysms. J Neurointerv Surg. 2020 Mar;12(3):298-302. doi: 10.1136/neurintsurg-2019-015173. Epub 2019 Sep 20.
• UCAS Japan Investigators; Morita A, Kirino T, Hashi K, Aoki N, Fukuhara S, Hashimoto N, Nakayama T, Sakai M, Teramoto A, Tominari S, Yoshimoto T. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med. 2012 Jun 28;366(26):2474-82. doi: 10.1056/NEJMoa1113260.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Actual): December 2, 2025
• Study Completion (Actual): December 2, 2025

Study Registration Dates

• First Submitted: February 11, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 14, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: stent; cerebral aneurysm; coil embolization; dual antiplatelet
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Thiophenes; Salicylates; Hydroxybenzoates; Ticlopidine; Thienopyridines; Clopidogrel; Aspirin
• Other Study ID Numbers: B-2102-667-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No