Ischemic Stroke, Atherosclerosis of Artery, Lipid Disorder, Statin
Conditions
Keywords
Probucol, Statin, Atherosclerosis, Ischemic stroke, Plaque burden, Lipid-lowering treatment
Brief summary
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.
Detailed description
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.
Interventions
DRUGStatin
Participants who opt for this group will receive guideline-recommended conventional lipid-lowering therapy. For those with a history of ischemic stroke (IS), myocardial infarction (MI), acute coronary syndrome within the past year, symptomatic peripheral artery disease, or two or more high-risk factors, the target LDL-C level will be set at 1.4 mmol/L. For other IS participants, the LDL-C target will be set at 1.8 mmol/L. All participants will receive moderate-intensity statin therapy as the primary treatment. If LDL-C levels are not adequately controlled, ezetimibe will be added. If lipid levels remain unsatisfactory, the addition of PCSK9 inhibitors will be considered. Moderate-intensity statins are defined as atorvastatin 10-20 mg or rosuvastatin 5-10 mg.
DRUGProbucol
Participants who choose this group will receive Probucol in combination with guideline-recommended lipid-lowering therapy. Specifically, participants in this group will take 0.5 grams of Probucol twice daily alongside the conventional lipid-lowering therapy mentioned in Group 1. The combination of Probucol and conventional therapy aims to further improve lipid profile and address atherosclerosis.
Sponsors
Xuanwu Hospital, Beijing
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older. 2. Diagnosed with ischemic stroke (IS) confirmed by cranial CT/MRI. 3. Onset of stroke within the last 30 days. 4. 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. 5. Signed informed consent.
Exclusion criteria
1. History of allergy to Probucol or statins. 2. Non-atherosclerotic arterial stenosis, such as vasculitis, moyamoya disease, or arterial dissection. 3. Potential cardiac embolic sources, such as atrial fibrillation, artificial heart valves, endocarditis, or patent foramen ovale. 4. Known bleeding tendencies or hemorrhagic diseases, such as thrombocytopenia (platelet count < 100 × 10\^9/L), hemorrhagic stroke, or gastrointestinal bleeding. 5. Severe myocardial diseases such as myocardial infarction (MI) or myocarditis. 6. 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. 7. Ventricular tachycardia, bradycardia, torsades de pointes, or syncopal episodes of cardiac origin. 8. Prolonged QT interval or conditions that may prolong the QT interval, such as certain medications. 9. Suffering from a severe illness with a life expectancy of less than one year or unable to cooperate due to cognitive or psychological issues. 10. 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. 11. Pregnant or breastfeeding individuals, those trying to conceive. 12. Concurrent participation in another clinical trial involving investigational drugs or devices within the past 30 days. 13. Planned surgery or intervention that would require discontinuation of the study medication during the study period. 14. Any reason, known to the participant and investigator, that would prevent the participant from adhering to the study protocol or follow-up. 15. Other conditions determined by the investigator that may require exclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plaque Burden from Baseline to 12-Month Follow-up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in High-Risk Plaque Count from Baseline to 12-Month Follow-up | Baseline to 12 months | The change in the number of high-risk plaques in the coronary, aortic, and carotid arteries, assessed via CTA at the 12-month follow-up compared to baseline. |
| Change in Atherosclerotic Burden Score from Baseline to 12-Month Follow-up | Baseline to 12 months | The change in the atherosclerotic burden score at 12 months, assessed through CTA imaging, compared to baseline. This score reflects the overall severity of atherosclerosis. |
| Occurrence of Cardiovascular Events at 12-Month and 24-Month Follow-up | 12 months and 24 months | The incidence of composite cardiovascular events, including new fatal cardiovascular events, myocardial infarction (MI), unstable angina requiring hospitalization, and ischemic stroke (IS). Events will be reported based on whichever occurs first during the 12-month and 24-month follow-up. |
| Poor Functional Outcome at 1-Month Follow-up | 1 month and 3 months | The occurrence of poor functional outcomes, defined as a modified Rankin Scale (mRS) score of ≥3, assessed during the first-month visit post-treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Biomarkers from Baseline to 12-Month Follow-up | Baseline to 12 months | This outcome will assess the changes in various biochemical and inflammatory biomarkers from baseline to the 12-month follow-up. The biomarkers to be evaluated include: Low-Density Lipoprotein Cholesterol (LDL-C) High-Sensitivity C-Reactive Protein (hsCRP) Lipoprotein(a) \[Lp(a)\] Total Cholesterol Apolipoprotein B (ApoB) Apolipoprotein A1 (ApoA1) Other relevant biomarkers |
Countries
China
Contacts
Primary ContactXin Ma, Doctor
Outcome results
None listed