RESCUE: PCSK9 Inhibitors for Carotid Vulnerable Plaque Remodeling

ConditionsAtherosclerosis Cerebral Carotid Plaque Vulnerable Plaque Carotid Stenosis

Trial statusNot yet recruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age40-80

SponsorKeqiang Zhao

About this trial

Carotid artery stenosis is a major cause of ischemic stroke. However, many strokes occur in patients with only mild-to-moderate stenosis. Evidence shows that it is not the degree of narrowing, but the "vulnerability" of the plaque-its internal composition-that determines rupture risk.

High-risk (vulnerable) plaques have a large lipid-rich necrotic core, a thin fibrous cap, and intraplaque hemorrhage. Statins can lower cholesterol and stabilize plaques, but some patients still experience progression or recurrent events.

PCSK9 inhibitors (such as evolocumab and alirocumab) are a new class of lipid-lowering drugs that reduce LDL cholesterol more strongly than statins alone. They may also have direct effects on the artery wall, improving plaque stability. Whether they can remodel vulnerable carotid plaques and how early this can be detected remains unclear.

This study uses high-resolution magnetic resonance imaging (HR-MRI), a non-invasive technique that visualizes plaque internal structure-including the lipid core, fibrous cap, and hemorrhage-to track changes over time.

Purpose: The RESCUE study aims to determine whether adding a PCSK9 inhibitor to standard statin therapy can remodel and stabilize vulnerable carotid plaques, and to detect these changes early using HR-MRI.

Design: This is a single-center, prospective, randomized, controlled, open-label trial with blinded endpoint evaluation (PROBE design). 120 adults with carotid vulnerable plaques will be enrolled at Beijing Tsinghua Chang Gung Hospital and randomly assigned 1:1 to: (1) Experimental group (n=60): statin PLUS PCSK9 inhibitor (subcutaneous injection); (2) Control group (n=60): statin alone. Follow-up is 24 months. HR-MRI is performed at baseline, 6, 12, and 24 months. Blood samples are collected for lipid and inflammatory markers. HR-MRI analysis is performed by blinded radiologists.

Primary Outcome: Change in lipid-rich necrotic core volume by HR-MRI at 12 and 24 months.

Secondary Outcomes: Fibrous cap thickness, intraplaque hemorrhage, remodeling index, LDL-C levels, inflammatory markers, and clinical events (stroke, TIA, cardiovascular death) over 24 months.

Status: Not yet recruiting. Planned start: January 2027. Conducted at Beijing Tsinghua Chang Gung Hospital, Beijing, China.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

. Carotid stenosis ≥30% detected by carotid ultrasound, not meeting criteria for surgical intervention, and confirmed presence of vulnerable plaque by HR-MRI (meeting any of the following: incomplete or thin fibrous cap <0.5 mm; lipid-rich necrotic core [LRNC] volume ≥40% of plaque volume; intraplaque hemorrhage [IPH]; or neovascularization).

Receiving standard statin therapy (moderate intensity or higher) for ≥3 months, with LDL-C still ≥1.8 mmol/L (70 mg/dL).

Willing to adhere to follow-up and provide signed informed consent.

Disqualifiers

Allergy or contraindication to PCSK9 inhibitors.

Active liver disease, myopathy, or creatine kinase (CK) elevation >5 times the upper limit of normal.

History of carotid revascularization (carotid endarterectomy [CEA] or carotid artery stenting [CAS]).

Renal insufficiency (estimated glomerular filtration rate [eGFR] <30 ml/min).

Trial design

Design model

Parallel

Treatments tested in this trial

Intervention 1
Drug
Evolocumab Description: 140 mg subcutaneous injection every 2 weeks. Dose may be adjusted based on LDL-C response per clinical judgment.
Intervention 3
Drug
Atorvastatin Description: 20 mg orally once daily. Dose titrated to achieve LDL-C target per guidelines.
Intervention 2
Drug
Alirocumab Description: 75 mg subcutaneous injection every 2 weeks. Dose may be adjusted based on LDL-C response per clinical judgment.
Intervention 4
Drug
Rosuvastatin Description: 10 mg orally once daily. Dose titrated to achieve LDL-C target per guidelines.

Treatment groups

120 Participants

are divided into 2 treatment groups

Group A: Experimental: Statin + PCSK9 InhibitorExperimental treatment 2 interventions

Group B: Active Comparator: Statin MonotherapyActive comparator 2 interventions

Trial outcomes

Primary outcomes

Change in lipid-rich necrotic core (LRNC) volume

Change from baseline in the volume of the lipid-rich necrotic core (LRNC) of the carotid plaque, measured by high-resolution magnetic resonance imaging (HR-MRI) at baseline, 6, and 12 months. LRNC volume is quantified using 3D multi-contrast HR-MRI sequences (including contrast-enhanced T1-weighted imaging) with semi-automated segmentation. The percentage change from baseline will also be reported.

Time frame