Low Dose Prasugrel vs Clopidogrel for Stenting or Flow Diverter for Unruptured Aneurysm

Low-dose Prasgurel Versus Clopidogrel on the Dual Antiplatelet Regimen for Intracranial Stenting or Flow Diverter Treatment for Unruptured Cerebral Aneurysms: a Multi-center Randomized Controlled Trial

Low clopidogrel response has been reported in about 5-44% of the total population, which is associated with an increase in thromboembolism.

Recently prasugrel drug widely accepted as a good option for these patients. The purpose of this study is to compare the safety and usefulness of prasugrel versus clopidogrel in patients who are scheduled to undergo stent or diverter treatment for non-ruptured cerebral aneurysms.

Study Overview

• Status: Recruiting
• Conditions: Intracranial Aneurysm
• Intervention / Treatment: Drug: Clopidogrel group; Drug: Prasugrel group

Detailed Description

Unruptured intracranial aneurysm (UIA) is a relatively common disease with a prevalence of about 1% of the total population. Widely accepted techniques of neuro-interventional therapy are coil embolization with or without stent deployment and flow diverter insertion. However, these two techniques inevitably had the risk of thromboembolism. For prevention and decrease, dual antiplatelet therapy is commonly used in the clinical field. However, clopidogrel does not produce normal metabolites due to various internal and external factors in the metabolic process in the liver and eventually fails to perform its original role of platelet activity suppression in many situations, called "clopidogrel hyporesponsive". Low clopidogrel response has been reported in about 5-44% of the total population, which is associated with an increase in thromboembolism.

Recently prasugrel drug widely accepted as a good option for these patients. The purpose of this study is to compare the safety and usefulness of prasugrel versus clopidogrel in patients who are scheduled to undergo stent or diverter treatment for non-ruptured cerebral aneurysms.

• Study Type: Interventional
• Enrollment (Anticipated): 406
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chang Ki Jang; Phone Number: 82-031-5189-8484; Email: changgeejang@yuhs.ac

Study Locations

• Korea, Republic of
  • Yongin-si
    • Gyeonggi-do, Yongin-si, Korea, Republic of, 16995
      • Recruiting
      • Yongin Severance Hospital, Yonsei University College of Medicine
      • Contact: Chang Ki Jang; Phone Number: 82-031-5189-8484; Email: changgeejang@yuhs.ac
      • Principal Investigator: Keun Young Park

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• UIAs without any evidence of rupture in intracranial imaging study within the last 6 months
• Planned treatment with coil embolization with stent insertion or flow diverter insertion
• If the patient himself/herself consented to this study

Exclusion Criteria:

• ∙ History of acute ischemic stroke or transient ischemic attack

  • Any intracranial hemorrhage except subarachnoid hemorrhage due to aneurysm rupture within the last 3 months
  • Concurrent treatment other than endovascular procedure (e.g. open craniotomy and microsurgical clipping)
  • Contraindications to iodine contrast agents
  • Already taking antiplatelet drugs or antithrombotic drugs other than aspirin
  • Hypersensitivity to aspirin, prasugrel or clopidogrel
  • Cardiac arrhythmia that should be needed to take anticoagulants
  • Pregnancy or lactating
  • Chronic kidney disease (< GFR 60)
  • Patients with chronic liver disease who have at least over 100 IU/L of either AST/ALT in the liver function test
  • Patients with pathological active bleeding, such as peptic ulcer
  • Patients with genetic problems, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption because they contain lactose
  • Patients continuously taking non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 inhibitors
  • Patients requiring concomitant administration of methotrexate 15 mg or more for one week
  • If it is judged difficult to follow up after treatment

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: Clopidogrel; Using a randomization program, the test group (203 patients; Aspirin 100 mg + Prasugrel 5 mg) and control group (203 patients; Aspirin 100 mg + Clopidogrel 75 mg) are classified. Prescribe the above drugs according to the assigned group, and take them 5 days before the procedure.	Drug: Clopidogrel group; Prescribe the drugs according to the assigned group, and take them 5 days before the procedure. Perform platelet function test (VerifyNow assay; Accumetrics, San Diego, California) one day before the procedure to check the P2Y12 reaction reactivity. And the hyporesponsive group patient is given pletaal 100mg once. And aspirin 100mg and clopidogrel 75mg mg will be maintained for 30 days.; Other Names: plavix
Active Comparator: prasugrel; Using a randomization program, the test group (203 patients; Aspirin 100 mg + Prasugrel 5 mg) and control group (203 patients; Aspirin 100 mg + Clopidogrel 75 mg) are classified. Prescribe the above drugs according to the assigned group, and take them 5 days before the procedure.	Drug: Prasugrel group; Prescribe the drugs according to the assigned group, and take them 5 days before the procedure. Perform platelet function test (VerifyNow assay; Accumetrics, San Diego, California) one day before the procedure to check the P2Y12 reaction reactivity. And the hyporesponsive group patient is given prasugrel 5mg once. And aspirin 100mg and prasugrel 5mg will be maintained for 30 days.; Other Names: effient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peri-procedural thromboembolic complications	thromboembolism detected during the neurointerventional procedure; transient ischemic attack or ischemic stroke or death with evidence of infarction on diffusion weighted imaging, which occurs within 30-days after procedureincidence of treatment-thromboembolic, TIA and death events.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
thromboembolic safety endpoint	Ischemic stroke on relevant arterial territory within 30days after procedure or any stroke; Diffusion restriction lesion detected on post-procedure 7 days MRIincidence of treatment-ischemic stroke on relevant territory and DWI lesion detected.	30days
bleeding safety endpoint	major and minor bleeding within 30days after procedure :: incidence of treatment-major and minor bleeding	30days

Collaborators and Investigators

• Sponsor: Yonsei University
• Collaborators: Gangnam Severance Hospital; Severance Hospital; Bucheon St. Mary's Hospital; International St. Mary's Hospital; Ewha Woman's University Seoul Hospital
• Investigators: Study Director: Chang Ki Jang, Yongin severance hospital,Yonsei university college of medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: January 9, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Actual): July 15, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Clopidogrel; Intracranial Aneurysm; Prasugrel Hydrochloride
• 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; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: S6700

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