A Prospective, Open-label Study Evaluating the Effects of Probucol Combined with Statins on Atherosclerotic Characteristics and Prognosis in Patients with Ischemic Stroke
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in Plaque Burden from Baseline to 12-Month Follow-up
研究概览
简要总结
The goal of this clinical trial is to evaluate whether the combination of Probucol with statin therapy can reduce the risk of vascular events and improve atherosclerosis outcomes in adults with ischemic stroke and confirmed atherosclerosis. The main questions it aims to answer are:
Does adding Probucol to statin therapy reduce plaque burden more effectively than statins alone? Does the combination therapy lead to fewer cardiovascular and cerebrovascular events compared to statins alone? Researchers will compare participants receiving standard statin therapy to those receiving statins combined with Probucol to assess differences in plaque burden and the occurrence of vascular events.
Participants will:
Choose either standard statin therapy (with possible addition of ezetimibe or PCSK9 inhibitors) or the same therapy combined with Probucol 0.5g twice daily.
Attend regular follow-up visits for monitoring atherosclerosis features and cardiovascular health over a 3-year period.
Undergo imaging studies to evaluate changes in atherosclerosis and blood tests to monitor lipid levels and other biomarkers.
详细描述
This single-center, prospective, open-label study will assess the effects of combining Probucol with statin therapy on the progression of atherosclerosis and the risk of vascular events in people with ischemic stroke. The primary hypothesis is that, in participants receiving guideline-recommended statin therapy, the addition of Probucol will reduce cardiovascular and cerebrovascular event risk, enhance plaque stability, and be well-tolerated.
The study will include participants aged 18 years or older who have experienced an ischemic stroke within the past 30 days and have confirmed atherosclerosis in any major artery (carotid, coronary, aortic, renal, or peripheral arteries). Participants will either follow a guideline-recommended lipid-lowering regimen (statins, with or without ezetimibe or PCSK9 inhibitors as needed) or a similar regimen combined with Probucol 0.5g twice daily. The study will enroll at least 100 participants in both the standard therapy group and the Probucol combination group.
Primary outcomes will include changes in plaque burden, while secondary outcomes will cover atherosclerotic features, composite vascular events (ischemic stroke, ischemic heart disease, vascular death), stroke recurrence, and poor functional prognosis (mRS ≥ 3). Exploratory outcomes will include changes in biochemical markers such as LDL-C, Ox-LDL, and Lp(a). Safety will be assessed by monitoring adverse events and serious adverse events.
Statistical analysis will include a multivariate linear regression model for primary outcomes, adjusted for baseline characteristics such as LDL-C levels and previous cardiovascular events. For time-to-event endpoints, Kaplan-Meier curves will be used, with Cox proportional hazards models providing hazard ratios. Subgroup analyses and repeated measures will further refine the understanding of treatment effects.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 years or older.
- •Diagnosed with ischemic stroke (IS) confirmed by cranial CT/MRI.
- •Onset of stroke within the last 30 days.
- •Evidence of atherosclerosis (AS) in at least one artery (carotid, coronary, aorta, renal, or peripheral arteries) identified through neck CTA, coronary CTA, or ultrasound examination of lower extremity arteries.
- •Signed informed consent.
排除标准
- •History of allergy to Probucol or statins.
- •Non-atherosclerotic arterial stenosis, such as vasculitis, moyamoya disease, or arterial dissection.
- •Potential cardiac embolic sources, such as atrial fibrillation, artificial heart valves, endocarditis, or patent foramen ovale.
- •Known bleeding tendencies or hemorrhagic diseases, such as thrombocytopenia (platelet count < 100 × 10^9/L), hemorrhagic stroke, or gastrointestinal bleeding.
- •Severe myocardial diseases such as myocardial infarction (MI) or myocarditis.
- •Liver (ALT or AST > twice the upper limit of normal) or kidney (creatinine > 1.5 times the upper limit of normal or glomerular filtration rate < 50 ml/min) dysfunction.
- •Ventricular tachycardia, bradycardia, torsades de pointes, or syncopal episodes of cardiac origin.
- •Prolonged QT interval or conditions that may prolong the QT interval, such as certain medications.
- •Suffering from a severe illness with a life expectancy of less than one year or unable to cooperate due to cognitive or psychological issues.
- •Use of Probucol or any lipid-lowering medication other than statins, ezetimibe, and PCSK9 inhibitors within the 30 days prior to enrollment, including bile acid sequestrants, fibrates, and other similar drugs.
- •Pregnant or breastfeeding individuals, those trying to conceive.
- •Concurrent participation in another clinical trial involving investigational drugs or devices within the past 30 days.
- •Planned surgery or intervention that would require discontinuation of the study medication during the study period.
- •Any reason, known to the participant and investigator, that would prevent the participant from adhering to the study protocol or follow-up.
- •Other conditions determined by the investigator that may require exclusion.
研究组 & 干预措施
Conventional Lipid-Lowering Therapy Group
Participants who choose this group will receive conventional lipid-lowering therapy following current clinical guidelines, which may include statins, ezetimibe, or PCSK9 inhibitors. The treatment regimen will be tailored to the participants' individual needs but will not include Probucol.
干预措施: Statin (Drug)
Combined Lipid-Lowering Therapy with Probucol Group
Participants who choose this group will receive a combination of conventional lipid-lowering therapy following current clinical guidelines (statins, ezetimibe, or PCSK9 inhibitors) and additional treatment with Probucol 0.5g twice daily. This regimen aims to further reduce atherosclerotic plaque burden and improve cardiovascular outcomes.
干预措施: Probucol (Drug)
结局指标
主要结局
Change in Plaque Burden from Baseline to 12-Month Follow-up
时间窗: Baseline to 12 months
The primary outcome is the change in atherosclerotic plaque burden, measured as the percentage of stenosis at the most severe location of atherosclerotic plaque on computed tomography angiography (CTA). Plaque burden is calculated as 100% × (diameter of the plaque at its most severe point/diameter of the arterial lumen). The difference between the baseline and the 12-month follow-up measurement will be used to assess the effectiveness of the treatment.
次要结局
- Change in High-Risk Plaque Count from Baseline to 12-Month Follow-up(Baseline to 12 months)
- Change in Atherosclerotic Burden Score from Baseline to 12-Month Follow-up(Baseline to 12 months)
- Occurrence of Cardiovascular Events at 12-Month and 24-Month Follow-up(12 months and 24 months)
- Poor Functional Outcome at 1-Month Follow-up(1 month and 3 months)
研究者
Xin Ma
Chief Doctor
Xuanwu Hospital, Beijing