Intensive Medical Therapy for High-risk Intracranial or Extracranial Arterial Stenosis

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Acute Stroke
Transient Ischemic Attack

Type

Interventional

Phase

Phase 3

Design

Allocation: RandomizedIntervention Model: Factorial AssignmentIntervention Model Description: The subjects are randomly assigned to the following four groups: Intensive antiplatelet therapy + immediate high-intensity statin therapy (80mg atorvastatin) Intensive antiplatelet therapy + delayed high-intensity statin therapy (40mg atorvastatin) Standard antiplatelet therapy + immediate high-intensity statin therapy (80mg atorvastatin) Standard antiplatelet therapy + delayed high-intensity statin therapy (40mg atorvastatin) Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Two nearly identical tablet forms of Clopidogrel (75mg Clopidogrel and matching placebo) with almost the same size, color and smell will be used in this research. Two nearly identical tablet forms of Aspirin (100mg Aspirin and matching placebo) with almost the same size, color and smell will be used in this research. Two nearly identical tablet forms of Atorvastatin (20mg Atorvastatin and matching placebo) with almost the same size, color and smell will be used in this research. Centers are not able to apply unblinding with biological experiment in this study. Researchers shall never unblind the code unless special situations occur such as Serious Adverse Events (SAE), which is essential for treatment. Clinical outcomes of efficacy and safety are submitted to Adjudication Committee, who should be blinded to randomization, for final determination.Primary Purpose: Treatment

Participation Requirements

Age: Between 35 years and 80 years
Gender: Both males and females

Description

Large-artery atherosclerotic stenosis is the main cause of ischemic stroke, especially in Asian population. However, targeted treatment evidence for large-artery atherosclerotic stenosis is limited according to the current guidelines. And also, randomized trial for statin therapy in patients with acute large arterial stenosis at early stage is still limited. The primary purpose of this study is to evaluate the efficacy and safety of intensive antiplatelet therapy versus standard antiplatelet therapy in reducing the risk of stroke at 90 days in patients with acute and high-risk symptomatic extracranial or intracranial arterial stenosis; the efficacy and safety of immediate high-intensity statin therapy (80mg atorvastatin) versus delayed high-intensity statin therapy (40mg atorvastatin) in reducing the risk of stroke at 90 days in patients with acute and high-risk symptomatic extracranial or intracranial arterial stenosis; and the efficacy and safety of intensive antiplatelet combined with immediate high-intensity statin therapy (80mg atorvastatin) versus standard antiplatelet combined with delayed high-intensity statin therapy (40mg atorvastatin) in reducing the risk of stroke at 90 days in patients with acute and high-risk symptomatic extracranial or intracranial arterial stenosis. This trial is a randomized, double-blind, placebo-controlled, multicenter, 2×2 factorial designed clinical trial. 6100 patients in 250 centers in China will be enrolled with one of the following situations (1) Mild ischemic stroke (NIHSS 4~5) within 24 hours of onset meets any of the following imaging conditions: a) Acute single cerebral infarction with criminal intracranial and extracranial atherosclerotic stenosis (stenosis rate ?50%),b) Acute multiple cerebral infarction (considered to be caused by large artery atherosclerosis, including non-stenotic vulnerable plaque);Or (2) Moderate-to-high-risk TIA (ABCD2?4) or mild ischemic stroke (NIHSS?5) within 24 to 72 hours of onset meets any of the following imaging conditions: a) Medium and high risk TIA with criminal intracranial and extracranial atherosclerotic stenosis (stenosis rate ?50%),b) Acute single cerebral infarction with criminal intracranial and extracranial atherosclerotic stenosis (stenosis rate ?50%),c) Acute multiple cerebral infarction (considered to be caused by large artery atherosclerosis, including non-stenotic vulnerable plaque) . Patients will be randomly assigned into 4 groups according to the ratio of 1:1:1:1: Intensive antiplatelet therapy + immediate high-intensity statin therapy (80mg atorvastatin) Intensive antiplatelet therapy + delayed high-intensity statin therapy (40mg atorvastatin) Standard antiplatelet therapy + immediate high-intensity statin therapy (80mg atorvastatin) Standard antiplatelet therapy + delayed high-intensity statin therapy (40mg atorvastatin) Face to face interviews will be made at baseline, 7, 14 (or hospital discharge), 90 ± 7 days and 12th month ± 14 days after randomization. Survival curves will be estimated for the primary outcome using the Kaplan-Meier procedure and compared using a Cox regression model Wald test, stratified by the opposite arm of the factorial design. Safety outcomes will be calculated using the Kaplan-Meier curve to simulate the 3-month cumulative risk, and the Cox proportional hazards model to calculate the HR and 95% confidence interval. Primary outcome is defined as stroke (including hemorrhagic and ischemic stroke). Secondary outcomes include composite vascular events (stroke, myocardial infarction, and cardiovascular death); ischemic stroke; transient ischemic attack; myocardial infarction; vascular death; all-cause death; poor functional outcome (mRS 2-6); and quality of life (EQ-5D scale). Safety outcomes, relating to antiplatelet therapy (i.e. bleeding, intracranial hemorrhage, and adverse events) and statin therapy (i.e. hepatotoxicity, muscle toxicity and adverse events) will be investigated.

Tracking Information

NCT #: NCT03635749
Collaborators: Ministry of Science and Technology of the People's Republic of China
Investigators: Principal Investigator: Yilong Wang, MD, PhD Beijing Tiantan Hospital