Efficacy of Probucol Combined with Statins Treatment for Ischemic Stroke (EPCIS)

March 20, 2025 updated by: Xin Ma, Xuanwu Hospital, Beijing

A Prospective, Open-label Study Evaluating the Effects of Probucol Combined with Statins on Atherosclerotic Characteristics and Prognosis in Patients with Ischemic Stroke

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Xicheng District, Beijing, China

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of hospitalized individuals diagnosed with ischemic stroke at the Stroke Center of Xuanwu Hospital. Participants will be adults aged 18 years and older who meet the inclusion criteria specified for the study.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Drug: Statin
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.
Other Names:
  • Conventional Lipid-Lowering Therapy
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.
Drug: Probucol
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.
Other Names:
  • Probucol and Statin Combination Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Plaque Burden from Baseline to 12-Month Follow-up
Time Frame: 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.
Baseline to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in High-Risk Plaque Count from Baseline to 12-Month Follow-up
Time Frame: 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.
Baseline to 12 months
Change in Atherosclerotic Burden Score from Baseline to 12-Month Follow-up
Time Frame: 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.
Baseline to 12 months
Occurrence of Cardiovascular Events at 12-Month and 24-Month Follow-up
Time Frame: 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.
12 months and 24 months
Poor Functional Outcome at 1-Month Follow-up
Time Frame: 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.
1 month and 3 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Biomarkers from Baseline to 12-Month Follow-up
Time Frame: 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
Baseline to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xuanwu Hospital, Beijing

Investigators

  • Principal Investigator: Jing Dong, Doctor, Xuanwu Hospital, Beijing

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2024

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

September 15, 2024

First Submitted That Met QC Criteria

September 17, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 20, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB [2024]275-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data will be available from the corresponding author upon reasonable request after the publication of the study results. Data will not be shared prior to publication.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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