Stent-Assisted Coiling Followed by Ticagrelor Monotherapy Instead of Dual Antiplatelet Therapy in Unruptured Intracranial Aneurysm (SAC-TIDE)

Stent-Assisted Coiling Followed by Ticagrelor Monotherapy Instead of Dual Antiplatelet Therapy in Endovascular Treatment of Unruptured Intracranial Aneurysm (SAC-TIDE) ---a Pilot Study

The primary goal of the trial is to investigate whether the experimental arms (receiving the P2Y12 inhibitor Ticagrelor) compared with the control arm (taking dual antiplatelet therapy) could reduce bleeding complications in patients with intracranial aneurysms undergoing Stent-Assisted Coiling.

Study Overview

• Status: Recruiting
• Conditions: Intracranial Aneurysm; Stent Complication
• Intervention / Treatment: Drug: Ticagrelor monotherapy; Drug: Dual Antiplatelet Therapy

Detailed Description

Bleeding complications associated with the use of DAPT have been of great concern, with up to one-third of PCI patients treated with DAPT previously reported to suffer from nuisance bleeding. Once any of these bleeding complications occur, adherence to the DAPT regimen may become difficult. Antiplatelet agents are necessary for patients undergoing stent-assisted spring coil embolisation of intracranial aneurysms and are key to reducing thrombosis leading to ischaemic stroke events in post-procedural patients.

Currently neither long-term DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory. Patients with aneurysms without underlying intracranial atherosclerotic disease have relatively lower ischaemic risk factors, and antiplatelet medication after stenting remains to be improved. Ticagrelor monotherapy was associated with a lower risk of major bleeding and no measurable increase in ischaemic events after a short course of 1- or 3-month DAPT. The study indicated no difference in stroke or death between mono- and dual-antiplatelet therapy after carotid artery placement, and P2Y12 inhibitor monotherapy may be an effective strategy to reduce severe bleeding complications while preserving ischemic benefits for patients. This study investigates the comparative efficacy and safety of stent-assisted coiling therapy for intracranial aneurysms after ticagrelor monotherapy as an alternative to dual antiplatelet therapy, to reduce the incidence of bleeding complications in patients, and thus to improve the antiplatelet strategy after stent-assisted coiling therapy for intracranial aneurysms.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hua Lu, Doctor; Phone Number: 18761671021; Email: luhua@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Hua Lu
      • Contact: Hua Lu, DR; Phone Number: luhua@njmu.edu.cn; Email: luhua@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Patients with a definitive diagnosis of an unruptured intracranial aneurysm with imaging suggestive of an aneurysm <10 mm
2. Patients who successfully underwent stent-assisted spring coil treatment for intracranial aneurysms without acute ischaemic or bleeding stroke events in the perioperative period
3. Age 18-60 years old
4. Patients with no previous history of chronic diseases such as hypertension, diabetes mellitus, coronary heart disease, hyperlipidaemia and so on
5. Agreed to participate in this study and gave informed consent for the collection and preservation of case data and the follow-up process.

Exclusion Criteria:

1. Planned surgery or intervention during the experiment requiring study drug discontinuation; (2) Contraindications requiring oral anticoagulation or aspirin or clopidogrel; (3) History of severe central nervous system damage (e.g., as a result of tumour, aneurysm, intracranial or spinal cord surgery); (4) Severe liver disease, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices), active hepatitis; (5 ) severe renal dysfunction (creatinine more than 1.5 times the upper limit of the normal range); (6) severe heart failure (NYHA class:III ~ IV); high risk for chronic arrhythmias (1st or 2nd degree atrioventricular block due to sinus node disease, bradycardic syncope without pacemaker); diagnosis or suspected diagnosis of acute coronary syndrome; bacterial endocarditis, pericarditis; (7) severe comorbidities or patients with active cancer with a life expectancy of less than 2 years; (8) participation in another clinical study using an experimental product within the past 30 days; currently receiving an experimental drug or device; and (9) pregnant, currently pregnant, or of childbearing potential without birth control or breastfeeding.

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
Experimental: ticagrelor monotherapy group; Ticagrelor monotherapy (starting dose of ticagrelor was a single loading dose of 180mg (90mg x 2 tablets) and thereafter 1 tablet (90mg) each time, twice daily.). After 1 month, continuation to ticagrelor monotherapy for 1 year.	Drug: Ticagrelor monotherapy; starting dose of ticagrelor was a single loading dose of 180mg (90mg x 2 tablets) and thereafter 1 tablet (90mg) each time, twice daily.
Active Comparator: Dual Antiplatelet Therapy group; Clopidogrel 75mg + Aspirin 100mg 1 month, after 1 month, change to aspirin 100mg 1 year.	Drug: Dual Antiplatelet Therapy; Clopidogrel 75mg + Aspirin 100mg 1 month, after 1 month, change to aspirin 100mg 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemorrhage	The incidence of bleeding defined by Bleeding Academic Research Consortium	Within one year after surgery
Composite endpoint of all-cause mortality, cerebrovascular accident or urgent target vessel revascularization.	Co-Primary Efficacy Endpoint (non-inferiority hypothesis)	Within one year after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ischemic stroke	ischemic stroke or death during 1 year of follow-up in an intention-to treat analysis.	This will be assessed during the first year of follow-up.
Stent thrombosis	Stent thrombosis	Within one year after surgery
BARC 1-5 type bleeding	bleeding defined by Bleeding Academic Research Consortium	Within one year after surgery

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Study Chair: Hua Lu, Doctor, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Ben-Dor I, Torguson R, Scheinowitz M, Li Y, Delhaye C, Wakabayashi K, Maluenda G, Syed AI, Collins SD, Gonzalez MA, Gaglia MA Jr, Xue Z, Kaneshige K, Satler LF, Suddath WO, Kent KM, Pichard AD, Waksman R. Incidence, correlates, and clinical impact of nuisance bleeding after antiplatelet therapy for patients with drug-eluting stents. Am Heart J. 2010 May;159(5):871-5. doi: 10.1016/j.ahj.2010.01.016.
• Kim KS, Fraser JF, Grupke S, Cook AM. Management of antiplatelet therapy in patients undergoing neuroendovascular procedures. J Neurosurg. 2018 Oct;129(4):890-905. doi: 10.3171/2017.5.JNS162307. Epub 2017 Dec 1.
• Nordeen JD, Patel AV, Darracott RM, Johns GS, Taussky P, Tawk RG, Miller DA, Freeman WD, Hanel RA. Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications. J Vasc Interv Neurol. 2013 Jun;6(1):26-34.
• Gutierrez J, Turan TN, Hoh BL, Chimowitz MI. Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2022 Apr;21(4):355-368. doi: 10.1016/S1474-4422(21)00376-8. Epub 2022 Feb 7. Erratum In: Lancet Neurol. 2022 Feb 16;:
• Valgimigli M, Mehran R, Franzone A, da Costa BR, Baber U, Piccolo R, McFadden EP, Vranckx P, Angiolillo DJ, Leonardi S, Cao D, Dangas GD, Mehta SR, Serruys PW, Gibson CM, Steg GP, Sharma SK, Hamm C, Shlofmitz R, Liebetrau C, Briguori C, Janssens L, Huber K, Ferrario M, Kunadian V, Cohen DJ, Zurakowski A, Oldroyd KG, Yaling H, Dudek D, Sartori S, Kirkham B, Escaned J, Heg D, Windecker S, Pocock S, Juni P; SIDNEY Collaboration. Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis. JACC Cardiovasc Interv. 2021 Feb 22;14(4):444-456. doi: 10.1016/j.jcin.2020.11.046.
• Jin Y, Huang H, Shu X, Chen S, Lu L, Gao X, Wu Z. P2Y12 inhibitor monotherapy and dual antiplatelet therapy after percutaneous coronary intervention: An updated meta-analysis of randomized trials. Thromb Res. 2021 Feb;198:115-121. doi: 10.1016/j.thromres.2020.11.038. Epub 2020 Dec 7.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ticagrelor; Intracranial Aneurysm; Stent-Assisted Coiling; Dual Antiplatelet
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: SAC-TIDE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) will be available to other researchers under the approval of the ethical committee.
• IPD Sharing Time Frame: the data will be available when summary data are published.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

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