A Cohort Study Comparing PCSK9 Inhibitor Plus Statin With Statin Monotherapy for Carotid Artery Stenosis

Official title

A Cohort Study Comparing PCSK9 Inhibitor Plus Statin With Statin Monotherapy for Carotid Artery Stenosis (TRIP-CAS)

Overview

A multicenter cohort study

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.

Interventions

• Drug PCSK9 inhibitor (biweekly injections) + Rosuvastatin/Atorvastatin ± Ezetimibe
  PCSK9 inhibitor (biweekly injections) + rosuvastatin/atorvastatin ± ezetimibe
• Drug Rosuvastatin/Atorvastatin ± Ezetimibe
  Rosuvastatin/atorvastatin ± ezetimibe

Primary outcome measures

• Change in plaque burden rate at the most stenotic carotid site at 180±7 days [Time frame: 180±7 days]

Secondary outcome measures (10)

• Lipid profile (TG/TC/LDL-C/HDL-C), liver function (ALT, AST), CK at 30±3 days [Time frame: 30±3 days]
• Lipid profile: TG/TC/LDL-C/HDL-C; liver function: ALT, AST, CK at 180±7 days [Time frame: 180±7 days]
• Plaque burden rate at the most stenotic cross-sectional site of the carotid artery at 180±7 days [Time frame: 180±7 days]
• Plaque diameter stenosis at 180±7 days [Time frame: 180±7 days]
• Plaque dimensions (length × thickness) at 180±7 days [Time frame: 180±7 days]
• Plaque stability (hypoechoic regions, fibrous cap integrity, ulceration, plaque score) at 180±7 days [Time frame: 180±7 days]
• mRS score at 180±7 days [Time frame: 180±7 days]
• Time to first major vascular event within 180±7 days (stroke/TIA, angina, myocardial infarction, symptomatic peripheral vascular disease) [Time frame: within 180±7 days]
• mRS score at 365±30 days [Time frame: 365±30 days]
• Time to first major vascular event within 365±30 days (stroke/TIA, angina, myocardial infarction, symptomatic peripheral vascular disease) [Time frame: within 365±30 days]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Changhai Hospital — Shanghai

Identifiers

NCT: NCT07036991 · TRIP-CAS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗