Efficacy of Probucol Combined with Statins Treatment for Ischemic Stroke

Recruiting

• Conditions: Ischemic Stroke; Lipid Disorder; Atherosclerosis of Artery; Statin
• Interventions: Drug: Statin; Drug: Probucol

• Registration Number: NCT06604117
• Lead Sponsor: Xuanwu Hospital, Beijing

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.

Study Timeline

• Study First Submitted: 2024-09-15
• Study First Submitted QC: 2024-09-17
• Study First Posted: 2024-09-19
• Study Start: 2024-10-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-25
• Primary Completion: 2027-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Conventional Lipid-Lowering Therapy Group	Statin	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.
Combined Lipid-Lowering Therapy with Probucol Group	Probucol	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Xuanwu Hospital; 🇨🇳 Xicheng District, Beijing, China