Clinical Trial of PCSK9 Inhibitor and Statin Treatment for Carotid Artery Stenosis
Phase 4
Not yet recruiting
- Conditions
- Carotid Artery Stenosis
- Interventions
- Drug: Evolocumab (biweekly injections) + Rosuvastatin/Atorvastatin ± EzetimibeDrug: Rosuvastatin/Atorvastatin ± Ezetimibe
- Registration Number
- NCT07036991
- Lead Sponsor
- Changhai Hospital
- Brief Summary
A prospective, multicenter, randomized controlled, open-label, blinded outcome evaluation (PROBE) trial.
- Detailed Description
The trial is to evaluate the effect of ultra-intensive lipid-lowering therapy (PCSK9 inhibitor + rosuvastatin or atorvastatin, with/without ezetimibe) versus conventional lipid-lowering therapy (rosuvastatin or atorvastatin, with/without ezetimibe) on changes in atherosclerotic burden in patients with carotid artery stenosis.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 406
Inclusion Criteria
Clinical inclusion criteria:
- Age ≥ 18 years.
- Asymptomatic mild-to-moderate carotid artery stenosis confirmed by CTA, MRA, ultrasound, or DSA, with no anticipated need for surgical intervention.
- Modified Rankin Scale (mRS) score ≤ 2
- Signed informed consent form obtained from the subject
Ultrasound Inclusion Criteria:
Carotid ultrasound showing a plaque burden rate ≥30% at the most stenotic cross-sectional site of the carotid artery (common carotid artery or proximal C1 segment of the internal carotid artery).
Exclusion Criteria
- Non-atherosclerotic carotid stenosis, including arterial dissection, Takayasu arteritis, radiation-induced vasculopathy, fibromuscular dysplasia, neurofibromatosis, suspected vasospasm, or recanalized vascular embolism.
- Known cardioembolic sources: mitral stenosis, mechanical heart valve, infective endocarditis, intracardiac thrombus/vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, chronic/paroxysmal atrial fibrillation. (Confound ASCVD outcome assessment.)
- History of cerebrovascular, coronary, or peripheral arterial endovascular intervention within 30 days before enrollment or anticipated surgery within the next 6 months.
- History of ischemic stroke, transient ischemic attack (TIA), or intracranial hemorrhage (parenchymal, subarachnoid, subdural, or epidural) before enrollment.
- Pre-existing intracranial tumor, cerebral aneurysm, or arteriovenous malformation.
- History of thromboembolic diseases (pulmonary embolism, mesenteric embolism, lower limb arterial embolism) or coronary atherosclerotic heart disease.
- Severe neurological deficits impairing independent living; diagnosed dementia/psychiatric disorders interfering with follow-up; or life expectancy <3 years due to other conditions.
- Severe/unstable comorbidities: Severe heart failure (NYHA Class III/IV or LVEF <30%), Renal failure (serum creatinine >264 μmol/L or creatinine clearance <0.6 mL/s), Severe hepatic dysfunction (ALT/AST >3× upper limit of normal), CK >5× upper limit of normal, Active malignancy.
- Use of PCSK9 inhibitors or CETP inhibitors within 24 weeks before enrollment.
- The subjects have taken strong inhibitor drugs of cytochrome P-450 3A4 (including: adagrasib, atazanavir, ceritinib, clarithromycin, darunavir, idelalisib, indinavir, itraconazole, ketoconazole, levonorgestrel, lonafarnib, lopinavir, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets), mbitasvir/paritaprevir/ritonavir and dasabuvir, posaconazole, co-formulations containing ritonavir and ritonavir itself, saquinavir, erythromycin, tucatinib, voriconazole) within one month before randomization, or may require such drugs during the study period.
- Pregnancy or lactation.
- Concurrent participation in another trial that may affect outcome assessment.
- Other situations that the investigator believes may cause significant harm to the subjects if they participate in this trial.
- Situations where the investigator believes there are other vascular lesions that may lead to short - term ischemic events and surgeries.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PCSK9 Inhibitor + Statin ± Ezetimibe Group Evolocumab (biweekly injections) + Rosuvastatin/Atorvastatin ± Ezetimibe PCSK9 inhibitor (biweekly injections) + rosuvastatin/atorvastatin ± ezetimibe, initiated on randomization day Statin ± Ezetimibe Group Rosuvastatin/Atorvastatin ± Ezetimibe Rosuvastatin/atorvastatin ± ezetimibe, continued or initiated on randomization day
- Primary Outcome Measures
Name Time Method Change in plaque burden rate at the most stenotic carotid site at 180±7 days 180±7 days
- Secondary Outcome Measures
Name Time Method Lipid profile (TG/TC/LDL-C/HDL-C), liver function (ALT, AST), CK, CRP at 30±3 days 30±3 days Lipid profile (TG/TC/LDL-C/HDL-C/Lp(a)/ApoA1/ApoB), liver function (ALT, AST), CK, CRP at 90±3 days 90±3 days Carotid plaque burden rate at 90±3 days 90±3 days Carotid plaque diameter stenosis at 90±3 days 90±3 days Carotid plaque dimensions (length × thickness) at 90±3 days 90±3 days Plaque stability (hypoechoic regions, fibrous cap integrity, ulceration, plaque score) at 90±3 days 90±3 days Lipid profile: TG/TC/LDL-C/HDL-C/Lp-a/ApoA1, ApoB; liver function: ALT, AST, CK, CRP at 180±7 days 180±7 days Plaque burden rate at the most stenotic cross-sectional site of the carotid artery at 180±7 days 180±7 days Plaque diameter stenosis at 180±7 days 180±7 days Plaque dimensions (length × thickness) at 180±7 days 180±7 days Plaque stability (hypoechoic regions, fibrous cap integrity, ulceration, plaque score) at 180±7 days 180±7 days mRS score at 180±7 days 180±7 days Time to first major vascular event within 180±7 days (stroke/TIA, angina, myocardial infarction, symptomatic peripheral vascular disease) within 180±7 days mRS score at 365±30 days 365±30 days Time to first major vascular event within 365±30 days (stroke/TIA, angina, myocardial infarction, symptomatic peripheral vascular disease) within 365±30 days