A Phase 4 interventional study of Intervention 1 and Intervention 3 in Atherosclerosis Cerebral, Carotid Plaque and Vulnerable Plaque, sponsored by Keqiang Zhao. Not yet recruiting. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by Keqiang Zhao · Phase 4, Interventional, and Treatment
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.
Background and Rationale
Carotid atherosclerotic plaque vulnerability, rather than the degree of luminal stenosis, is the primary determinant of ischemic stroke risk. High-resolution magnetic resonance imaging (HR-MRI) has emerged as a powerful non-invasive tool capable of characterizing plaque components in vivo, including the lipid-rich necrotic core (LRNC), fibrous cap integrity, intraplaque hemorrhage (IPH), and neovascularization. These imaging biomarkers provide critical insights into plaque phenotype and natural history.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as a class of potent lipid-lowering agents, have demonstrated substantial efficacy in reducing low-density lipoprotein cholesterol (LDL-C) levels and improving cardiovascular outcomes. Beyond their established lipid-lowering effects, emerging evidence suggests that PCSK9 inhibitors may exert direct pleiotropic effects on plaque stabilization, including promoting fibrous cap thickening, reducing intraplaque inflammation, and facilitating lipid regression. However, the temporal dynamics of PCSK9 inhibitor-induced plaque remodeling and their quantitative relationship with LDL-C reduction remain incompletely understood, particularly in the carotid territory.
Study Hypothesis
The RESCUE study hypothesizes that, compared with standard statin monotherapy, the addition of a PCSK9 inhibitor to statin therapy will result in more favorable remodeling of carotid vulnerable plaques, characterized by a significant reduction in LRNC volume, fibrous cap thickening, regression of neovascularization, and decreased incidence of IPH, as quantitatively assessed by HR-MRI. Furthermore, we hypothesize that specific HR-MRI-derived imaging biomarkers at early time points (e.g., 3 or 6 months) can predict long-term plaque stabilization.
Study Design Overview
RESCUE is a single-center, prospective, randomized, open-label, blinded endpoint evaluation (PROBE) trial designed to test these hypotheses. A total of 120 eligible participants with carotid vulnerable plaques will be randomly assigned in a 1:1 ratio to either the experimental group (statin plus PCSK9 inhibitor) or the control group (statin monotherapy). The study employs a PROBE design to balance operational feasibility with objectivity in endpoint assessment: while treatment allocation is open-label, all HR-MRI analyses and clinical endpoint adjudications will be performed by independent, blinded readers.
Key Methodological Considerations
HR-MRI Protocol and Analysis: A standardized multi-sequence HR-MRI protocol (including T1-weighted, T2-weighted, and contrast-enhanced sequences) will be applied at baseline, 6, 12, and 24 months. Quantitative measurements of plaque components will follow predefined, reproducible criteria. Image analysis will be conducted by two experienced radiologists blinded to treatment allocation and clinical data, with inter-reader reliability assessed.
Temporal Profiling: Serial imaging at 5 time points (baseline, 3, 6, 12, and 24 months) allows for the characterization of the temporal sequence of plaque compositional changes and their correlation with serial LDL-C levels, enabling the exploration of a dose-response relationship between lipid lowering and plaque remodeling.
Early Prediction: By leveraging machine learning or multivariate statistical approaches on early-phase HR-MRI data, the study aims to identify imaging signatures that predict long-term plaque stabilization, addressing a critical unmet need in personalized management of carotid atherosclerosis.
Significance
RESCUE will provide high-level evidence on the efficacy of PCSK9 inhibitors in reshaping carotid vulnerable plaques and establish an HR-MRI-based framework for early prediction of treatment response. The findings are expected to inform future clinical guidelines and support the development of imaging-guided therapeutic strategies for stroke prevention.
102 studies on the registry are indexed under Intracranial Arteriosclerosis; 48 are open to participants now.
This study's planned enrollment of 120 is below the median of 194 across 61 interventional studies indexed under Intracranial Arteriosclerosis.
Browse Intracranial Arteriosclerosis studies →This is the only study on the registry with Keqiang Zhao as lead sponsor.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive standard statin therapy (either atorvastatin 20 mg or rosuvastatin 10 mg orally once daily, dose-adjusted to achieve target LDL-C) plus a PCSK9 inhibitor (either evolocumab 140 mg subcutaneously every 2 weeks or alirocumab 75 mg subcutaneously every 2 weeks, dose-adjusted per protocol). Treatment duration is 24 months. HR-MRI assessments will be performed at baseline, 3, 6, 12, and 24 months.
Drug: Intervention 1 · Drug: Intervention 2
Participants will receive standard statin monotherapy (either atorvastatin 20 mg or rosuvastatin 10 mg orally once daily, dose-adjusted to achieve target LDL-C) without PCSK9 inhibitor. Treatment duration is 24 months. HR-MRI assessments will be performed at baseline, 3, 6, 12, and 24 months.
Drug: Intervention 3 · Drug: Intervention 4
Evolocumab Description: 140 mg subcutaneous injection every 2 weeks. Dose may be adjusted based on LDL-C response per clinical judgment.
Also known as: Repatha
Atorvastatin Description: 20 mg orally once daily. Dose titrated to achieve LDL-C target per guidelines.
Also known as: Lipitor
Alirocumab Description: 75 mg subcutaneous injection every 2 weeks. Dose may be adjusted based on LDL-C response per clinical judgment.
Rosuvastatin Description: 10 mg orally once daily. Dose titrated to achieve LDL-C target per guidelines.
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: Baseline, 6 months, and 12 months
Change in fibrous cap thickness
Change from baseline in the thickness of the fibrous cap of the carotid plaque, measured by high-resolution magnetic resonance imaging (HR-MRI) at baseline, 6, and 12 months. Fibrous cap thickness is quantified at the thinnest point of the plaque using 3D multi-contrast HR-MRI sequences with semi-automated segmentation and same-plaque longitudinal co-registration. The percentage change from baseline will also be reported.
Time frame: Baseline, 6 months, and 12 months
Change in intraplaque hemorrhage
Change in intraplaque hemorrhage (volume or signal characteristics) of the carotid plaque, as measured by high-resolution magnetic resonance imaging (HR-MRI) at 6 months, and 12 months
Time frame: Baseline, 6 months, and 12 months
Change from baseline in low-density lipoprotein cholesterol (LDL-C) levels
Change from baseline in low-density lipoprotein cholesterol (LDL-C) levels, measured from fasting venous blood samples at baseline, 6, and 12 months. LDL-C is quantified using standard enzymatic assays (or homogeneous direct method). The percentage change from baseline and the proportion of participants achieving target LDL-C (\<1.4 mmol/L or per protocol) will also be reported.
Time frame: Baseline, 6 months, and 12 months
Serum concentrations of inflammatory markers (hs-CRP, IL-6) at baseline, 6, and 12 months
Serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) measured at baseline, 6 months, and 12 months. Change from baseline will also be calculated.
Time frame: Baseline, 6 months, and 12 months
Number of participants with clinical events (ischemic stroke, transient ischemic attack [TIA], or cardiovascular death)
Number of participants experiencing a composite endpoint of ischemic stroke, transient ischemic attack (TIA), or cardiovascular death during the follow-up period, assessed at 6, 12, and 24 months.
Time frame: 6 months, and 12 、24months
Performance of machine learning model for predicting plaque stabilization
Predictive performance (e.g., area under the curve \[AUC\], sensitivity, specificity) of the machine learning model integrating baseline and follow-up HR-MRI features with clinical and laboratory parameters for identifying plaque stabilization at 24 months.
Time frame: 24 months
No study locations are listed for this record.
Plan to share: No — No plan to share individual participant data at this time. Data sharing arrangements will be determined upon study completion, subject to ethics approval, informed consent provisions, and data privacy regulations.
Start is estimated for Jan 2027; primary completion for Jan 2029, 24 months later.
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Studies of the drug tested here: Evolocumab
Intracranial Arteriosclerosis →