Tirofiban for Reduction of Thromboembolic Events in Endovascular Unruptured Aneurysm Repair (TEAR)

Prophylactic Administration of Tirofiban for Preventing Thromboembolic Events in Stent-assisted Coiling and Flow Diversion Treatments of Unruptured Intracranial Aneurysms

To explore whether administering tirofiban in stent-assisted coiling/flow diverting treatments for participants with unruptured intracranial aneurysms can reduce new ischemic lesions on postoperative DWI sequences compared to conventional dual antiplatelet therapy.

Study Overview

• Status: Recruiting
• Conditions: Unruptured Intracranial Aneurysm; Thromboembolic Events; Flow Diverter; Stent-assisted Coiling
• Intervention / Treatment: Drug: Tirofiban; Drug: aspirin, clopidogrel

Detailed Description

This is a single-center, open-label, assessor-blinded randomized controlled trial. Participants with stent-assisted coiling/flow diverting for unruptured intracranial aneurysms will be enrolled and randomized into two groups: Tirofiban group-after femoral artery puncture, initial infusion of 0.4μg/kg body weight/minute over 30 minutes, followed by a continuous infusion of 0.1μg/kg body weight/minute for 24 hours. Meanwhile, routine dual antiplatelet therapy (aspirin 100 mg/day, clopidogrel 75 mg/day) will be administered. Placebo group-100 mg/day aspirin and 75 mg/day clopidogrel. The primary effectiveness endpoint is the numbers and volumes of ischemic lesions on diffusion weighted imaging (DWI) within 48 hours after procedure.

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Qianmei Jiang; Phone Number: 13882701231; Email: 13882701231@163.com
• Study Contact Backup: Name: Lian Liu; Email: liuliandaxiang@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital
    • Contact: Jing Jing; Email: jingj_bjttyy@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages 18-80.
2. Participants with unruptured cerebral aneurysms eligible for stent-assisted coiling or flow diversion devices.
3. Completement of preoperative antiplatelet preparation.
4. Signed informed consent.

Exclusion Criteria:

1. Abnormal platelet count (normal reference is 100-300×10^9/L).
2. Allergy to study drugs and anesthetics.
3. Contradictory to MRI examination.
4. Known history of intracranial tumor, arteriovenous malformation, arteriovenous fistula, venous sinus thrombosis, hereditary cerebral small vessel disease, peripheral hemangioma (e.g., aortic aneurysm, limb vascular aneurysm).
5. Known history of cerebral parenchymal hemorrhage, subarachnoid hemorrhage, cerebral infarction, transient ischemic attack, or gastrointestinal bleeding within 6 months.
6. Clear indications for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis).
7. Antiplatelet drug (exclude aspirin and clopidogrel) being taken within 72 hours; anticoagulant drug (including heparin or oral anticoagulants) being taken within 10 days;
8. Participants with recurrent aneurysms who have received neurointerventional treatment.
9. Inability to follow endovascular procedures due to anatomical difficulties.
10. Severe renal (creatinine exceeding 1.5 times of the upper limit of normal range) or hepatic (ALT or AST > twice the upper limit of normal range) insufficiency.
11. Severe heart failure (NYHA classes III and IV) or severe arrhythmias, including sick sinus syndrome, severe atrioventricular block, and bradycardia-related syncope.
12. Pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirofiban group; After femoral artery puncture, initial infusion of 0.4μg/kg body weight/minute over 30 minutes, followed by a continuous infusion of 0.1μg/kg body weight/minute for 24 hours.	Drug: Tirofiban; Initial infusion of 0.4μg/kg body weight/minute over 30 minutes, followed by a continuous infusion of 0.1μg/kg body weight/minute for 24 hours.; Drug: aspirin, clopidogrel; aspirin 100 mg/day, clopidogrel 75 mg/day
Placebo Comparator: Standard medical care; Routine dual antiplatelet therapy (aspirin 100 mg/day, clopidogrel 75 mg/day)	Drug: aspirin, clopidogrel; aspirin 100 mg/day, clopidogrel 75 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The volumes of ischemic lesions on diffusion weighted imaging within 48 hours after procedure.	within 48 hours after procedure
The numbers of ischemic lesions on diffusion weighted imaging within 48 hours after procedure.	within 48 hours after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any new stroke events (ischemic stroke or hemorrhagic stroke) within 48-hour and 30-day after procedure.		at postoperative 48-hour and 30-day
Incidence of ischemic stroke within 48-hour and 30-day after procedure.		at postoperative 48-hour and 30-day
Incidence of transient ischemic attack within 48-hour and 30-day after procedure.		at postoperative 48-hour and 30-day
Incidence of ischemic stroke and transient ischemic attack within 48-hour and 30-day after procedure.		at postoperative 48-hour and 30-day
Disabling stroke within 30-day after procedure.	Disabling stroke is defined as modified Rankin Scale score >1. The modified Rankin Scale score ranges from 0 to 6, and the higher the score, the greater the degree of disability.	at postoperative 30-day

Other Outcome Measures

Outcome Measure	Time Frame
Moderate and severe bleeding events according to the GUSTO criteria within 48-hour after procedure.	at postoperative 48-hour
Moderate and severe bleeding events according to the GUSTO criteria within 30-day after procedure.	at postoperative 30-day
All bleeding events (severe/moderate bleeding and intracranial hemorrhage) within 48-hour and 30-day after procedure.	at postoperative 48-hour and 30-day
Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 48-hour and 30-day after procedure.	at postoperative 48-hour and 30-day
Total mortality within 48-hour and 30-day after procedure.	at postoperative 48-hour and 30-day
Adverse events/Severe adverse events reported by investigators within 48-hour and 30-day after procedure.	at postoperative 48-hour and 30-day

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Study Chair: Jing Jing, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Embolism and Thrombosis; Intracranial Arterial Diseases; Thromboembolism; Aneurysm; Intracranial Aneurysm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel; Tirofiban
• Other Study ID Numbers: CSA2022KY009

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