Clinical Trial of PCSK9 Inhibitor and Statin Treatment for Carotid Artery Stenosis (TRIP-CAS)

Naval Military Medical University

Status and phase: Not yet enrolling; Phase 4

Conditions: Carotid Artery Stenosis

Treatments: Drug: Evolocumab (biweekly injections) + Rosuvastatin/Atorvastatin ± Ezetimibe; Drug: Rosuvastatin/Atorvastatin ± Ezetimibe

Study type: Interventional

Funder types: Other

Identifiers

NCT07036991

TRIP-CAS

Details and patient eligibility

About

A prospective, multicenter, randomized controlled, open-label, blinded outcome evaluation (PROBE) trial.

Full 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.

Enrollment: 406 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Clinical inclusion criteria:

1. Age ≥ 18 years.
2. Asymptomatic mild-to-moderate carotid artery stenosis confirmed by CTA, MRA, ultrasound, or DSA, with no anticipated need for surgical intervention.
3. Modified Rankin Scale (mRS) score ≤ 2
4. 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

1. Non-atherosclerotic carotid stenosis, including arterial dissection, Takayasu arteritis, radiation-induced vasculopathy, fibromuscular dysplasia, neurofibromatosis, suspected vasospasm, or recanalized vascular embolism.
2. 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.)
3. History of cerebrovascular, coronary, or peripheral arterial endovascular intervention within 30 days before enrollment or anticipated surgery within the next 6 months.
4. History of ischemic stroke, transient ischemic attack (TIA), or intracranial hemorrhage (parenchymal, subarachnoid, subdural, or epidural) before enrollment.
5. Pre-existing intracranial tumor, cerebral aneurysm, or arteriovenous malformation.
6. History of thromboembolic diseases (pulmonary embolism, mesenteric embolism, lower limb arterial embolism) or coronary atherosclerotic heart disease.
7. Severe neurological deficits impairing independent living; diagnosed dementia/psychiatric disorders interfering with follow-up; or life expectancy <3 years due to other conditions.
8. 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.
9. Use of PCSK9 inhibitors or CETP inhibitors within 24 weeks before enrollment.
10. 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.
11. Pregnancy or lactation.
12. Concurrent participation in another trial that may affect outcome assessment.
13. Other situations that the investigator believes may cause significant harm to the subjects if they participate in this trial.
14. Situations where the investigator believes there are other vascular lesions that may lead to short - term ischemic events and surgeries.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

406 participants in 2 patient groups

PCSK9 Inhibitor + Statin ± Ezetimibe Group

Experimental group

Description:

PCSK9 inhibitor (biweekly injections) + rosuvastatin/atorvastatin ± ezetimibe, initiated on randomization day

Treatment:

Drug: Evolocumab (biweekly injections) + Rosuvastatin/Atorvastatin ± Ezetimibe

Statin ± Ezetimibe Group

Active Comparator group

Description:

Rosuvastatin/atorvastatin ± ezetimibe, continued or initiated on randomization day

Treatment:

Drug: Rosuvastatin/Atorvastatin ± Ezetimibe