Probucol for Symptomatic Intracranial and Extracranial Artery Stenosis

Official title

A Multicenter, Double-blind, Placebo-controlled, Randomized Clinical Trial of Probucol in Reducing the Risk of Recurrent Stroke in Patients With Symptomatic Intracranial and Extracranial Large-artery Stenosis

Overview

This study is a multicenter, double-blind, placebo-controlled, randomized clinical trial that aims to evaluate the efficacy of probucol on the reduction of the risk of recurrent stroke in patients with symptomatic intracranial or extracranial arterial stenosis.

Detailed description

This study is a multicenter, double-blind, placebo-controlled, randomized clinical trial that aims to evaluate the efficacy of probucol on the reduction of the risk of recurrent stroke in patients with symptomatic intracranial or extracranial arterial stenosis. During the study period, 5452 patients at intermediate risk for ischemic stroke or TIA will be enrolled from 100 centers.To evaluate whether probucol, as compared with placebo, reduces the risk of recurrent stroke in patients at high risk for ischemic stroke or TIA within 7 days of onset.Patients in one arm will receive probucol initiated with a dose of 1000 mg per day on days 1 through 30, and continuing with 500 mg per day after day 31, and those in the other arm will receive an equivalent placebo drug. Study visits will be performed on the day of randomization, at discharge, at day 90 and at 1 year and then followed up annually until the occurrence of the endpoint event or the end of the study. In addition, patients will be followed up at any time when new clinical symptoms of the neurologic system and suspicious events occur, including worsening of the original ischemic event and the appearance of new transient or persistent neurologic symptoms.

Interventions

• Drug Probucol
  Inclusion Days 1-30: Probucol 1000mg/day (500mg per dose, twice daily, a minimum of 4 hours should elapse between each pair of doses.) Inclusion Days 31 and beyond: Probucol 500mg/day (250mg per dose, twice daily, a minimum of 4 hours should elapse between each pair of doses.)
• Drug Placebo probucol
  Inclusion Days 1-30: Placebo Probucol 1000mg/day (500mg per dose, twice daily, a minimum of 4 hours should elapse between each pair of doses.) Inclusion Days 31 and beyond: Placebo Probucol 500mg/day (250mg per dose, twice daily, a minimum of 4 hours should elapse between each pair of doses.)

Primary outcome measures

• Recurrent stroke event [Time frame: within 1 year]

Secondary outcome measures (4)

• Recurrent ischemic stroke event [Time frame: within 1 year]
• Composite vascular events [Time frame: within 1 year]
• Poor functional outcome [Time frame: within 1 year]
• All-cause mortality [Time frame: within 1 year]

Eligibility criteria

Inclusion criteria

1.40 years or older than 40 years; 2.Ischemic stroke or transient ischemic attack (TIA); 3.Within 7 days from onset to randomization; 4.Main intracranial or extracranial arteries supplying the ischemic event region are narrowed by more than 50%; 5.Informed consent signed.

Exclusion criteria

• Presumed cardiac source of embolus, such as atrial fibrillation, prosthetic cardiac valve, endocarditis or patent foramen ovale;
• Stroke/TIA due to arterial dissection, angioplasty, or vascular surgery;
• Usage of probucol within 30 days before randomization;
• Known allergy or sensitivity or intolerance to probucol;
• Myocardial disease within the past 30 days, including myocardial infarction, myocarditis;
• With ventricular tachycardia, bradycardia, tip-twist ventricular tachycardia；
• With Q-Tc interval prolongation, or currently using drugs that may cause Q-Tc interval prolongation (male Q-Tc>450ms, female Q-Tc>470ms);
• Cardiac syncope or unexplained syncope;
• Impaired hepatic (ALT or AST > twice the upper limit of normal range) or kidney (creatinine exceeding 1.5 times of the upper limit of normal range or eGFR less than 50 ml/min) function at randomization;
• Anemia (haemoglobin <10g/dL), thrombocytopenia (platelet count <100×109/L) or leucopenia (white blood cell <3×109/L) at randomization;
• Planned surgery or interventional treatment requiring cessation of the study drug during the study;
• Participating in another clinical trial with an investigational drug or device concurrently or during the last 30 days;
• Pregnant or lactating women; Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control;
• Severe non-cardiovascular comorbidity with a life expectancy of less than 1 years;
• Serious drug or alcohol abuse in the past 1 year；
• Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders, or to be an unsuitable candidate for the study for any other considered by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affliated Hospital of Wannan Medical College — Wuhu

Identifiers

NCT: NCT06225752 · 2023AH040246

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗