PCSK9 Inhibitor with Statin Therapy for Asymptomatic Intracranial Atherosclerosis

Launched by PEKING UNION MEDICAL COLLEGE HOSPITAL · Mar 24, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for people with asymptomatic intracranial atherosclerosis, which is a condition where blood vessels in the brain become narrowed due to plaque buildup. The research is comparing two treatments: one group will receive a combination of a PCSK9 inhibitor (a type of medication that lowers cholesterol) and a statin (another cholesterol-lowering drug), while the other group will only receive the statin. The goal is to see if the combination therapy is more effective in reducing plaque in the blood vessels of the brain, which will be monitored using advanced imaging techniques.

To be eligible for this trial, participants need to be between 18 and 60 years old and have a significant narrowing (50% to 99%) of specific brain arteries confirmed by imaging tests, without any history of strokes or related events. Participants should also have high cholesterol levels. The trial is not yet recruiting, meaning it hasn’t started enrolling participants yet, but once it does, those who qualify can expect regular check-ups and advanced imaging to monitor their condition. It’s important to note that there are several criteria that could exclude someone from participating, including certain medical conditions, recent surgeries, or current medications that may interfere with the trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age ≥18 and ≤60, male or female;
• • 2. Asymptomatic intracranial artery stenosis (50%-99%) in the internal carotid artery (C6-7 segments), middle cerebral artery (M1 segment), vertebral artery (V4 segment), or basilar artery, confirmed by angiography (MRA, CTA, or DSA);
• • 3. Atherosclerosis identified as the cause of intracranial artery stenosis by high-resolution magnetic resonance imaging;
• • 4. No previous ischemic cerebrovascular events (including ischemic stroke or transient ischemic attack).
• • 5. Baseline low-density lipoprotein cholesterol ≥ 2.6 mmol/L;
• • 6. Informed consent signed.
• Exclusion Criteria:
• • 1. Non-atherosclerotic intracranial artery stenosis, including arterial dissection; moya moya disease; systemic vasculitis and primary central nervous system vasculitis; varicella-zoster vasculopathy or other viral vasculopathy; neurosyphilis and other intracranial infections, radiation vasculopathy; fibromuscular dysplasia, sickle cell disease, neurofibromatosis; reversible cerebral vasoconstriction syndrome; postpartum vasculopathy; suspected vasospasm, suspected reperfusion after vessel occlusion.
• • 2. Upstream tandem extracranial vessel stenosis (≥50%) adjacent to the target intracranial stenotic vessel.
• • 3. Previous treatment of target intracranial lesion with endovascular intervention or plan to perform endovascular intervention within 6 months, including intracranial stenting, endovascular angioplasty, and thrombectomy.
• • 4. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, extradural) within 90 days prior to enrollment.
• • 5. Presence of intracranial tumors.
• • 6. Presence of cerebral aneurysms, or arteriovenous malformations with indications for interventional therapy.
• • 7. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 6 months after enrollment.
• • 8. Presence of any of the following unequivocal cardiac sources of embolism: mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, chronic or paroxysmal atrial fibrillation.
• • 9. New York Heart Association (NYHA) class III or IV, or known left ventricular ejection fraction \< 30%.
• • 10. AST and/or ALT \> 3 times the ULN; creatinine clearance \< 0.6 mL/s and/or serum creatinine \> 265 μmol/L (\>3.0 mg/dL); CK \>5 times the ULN at screening.
• • 11. Retinal hemorrhage Active bleeding diathesis or coagulopathy; active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count \<125,000, hematocrit \<30, Hgb \<10 g/dl, uncorrected INR \>1.5, bleeding time \>1 minute beyond ULN at screening, or heparin associated thrombocytopenia that increases the risk of bleeding.
• • 12. Presence of systemic autoimmune diseases: systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, Behçet's disease, mixed connective tissue disease, IgG4-related disease.
• • 13. Dementia or psychiatric problem that hinder their ability to consistently adhere to an outpatient program. Co-morbid conditions that may limit the life expectancy to less than 3 years.
• • 14. Relative/absolute contraindications to magnetic resonance imaging (MRI) (such as presence of internal metallic objects, claustrophobia, contrast agent allergy, severe renal impairment, epilepsy, hypotension, asthma, and other hypersensitivity respiratory diseases).
• • 15. Uncontrolled hypertension during the screening period, defined as seated systolic blood pressure (SBP) \> 180 mmHg or diastolic blood pressure (DBP) \> 110 mmHg.
• • 16. Prior use of PCSK9 inhibitor before this recruitment.
• • 17. Known intolerance or allergy to statin.
• • 18. Pregnancy, lactation, or planning pregnancy.
• • 19. Currently participating in another study.