[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100656106":3},{"organization":4,"outcomesModule":7,"designInfo":35,"detailedDescription":46,"studyPopulation":40,"armGroups":47,"interventions":62,"overallOfficials":84,"centralContacts":88,"locations":40,"responsibleParty":94,"collaborators":40,"id":98,"slug":99,"hasResults":100,"nctId":101,"briefTitle":102,"officialTitle":103,"acronym":104,"eligibilityCriteria":105,"healthyVolunteers":100,"sex":106,"minAge":107,"maxAge":108,"enrollmentInfo":109,"targetDuration":40,"studyType":112,"phases":113,"briefSummary":115,"conditions":116,"keywords":121,"overallStatus":129,"whyStopped":40,"lastUpdateSubmitDate":130,"lastUpdatePostDateStruct":131,"startDateStruct":134,"completionDateStruct":136,"leadSponsor":138,"locationsCount":40},{"fullName":5,"class":6},"Beijing Tsinghua Chang Gung Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":19,"otherOutcomes":30},[9,13,16],{"measure":10,"description":11,"timeFrame":12},"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.","Baseline, 6 months, and 12 months",{"measure":14,"description":15,"timeFrame":12},"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.",{"measure":17,"description":18,"timeFrame":12},"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",[20,23,26],{"measure":21,"description":22,"timeFrame":12},"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 (\\\u003C1.4 mmol\u002FL or per protocol) will also be reported.",{"measure":24,"description":25,"timeFrame":12},"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.",{"measure":27,"description":28,"timeFrame":29},"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.","6 months, and 12 、24months",[31],{"measure":32,"description":33,"timeFrame":34},"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.","24 months",{"allocation":36,"interventionModel":37,"interventionModelDescription":38,"primaryPurpose":39,"observationalModel":40,"timePerspective":40,"maskingInfo":41},"RANDOMIZED","PARALLEL","The RESCUE study employs a prospective, randomized, open-label, blinded endpoint evaluation (PROBE) design with parallel assignment. Eligible participants are randomly allocated in a 1:1 ratio to either the experimental group (statin plus PCSK9 inhibitor) or the control group (statin monotherapy). Both groups are followed in parallel for 24 months with serial HR-MRI assessments at baseline, 3, 6, 12, and 24 months. Although treatment allocation is open-label, all imaging analyses and clinical endpoint adjudications are performed by independent readers blinded to group assignment, ensuring objective evaluation of plaque remodeling outcomes.","TREATMENT",null,{"masking":42,"maskingDescription":43,"whoMasked":44},"SINGLE","This study uses a PROBE (Prospective, Randomized, Open-label, Blinded Endpoint) design. Participants and care providers are unmasked to treatment allocation. Outcome assessors (radiologists interpreting HR-MRI images) and data analysts are masked to group assignment. All HR-MRI analyses and clinical endpoint adjudications are performed by independent readers who are blinded to treatment allocation and clinical data.",[45],"OUTCOMES_ASSESSOR","Background and Rationale\n\nCarotid 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.\n\nProprotein convertase subtilisin\u002Fkexin 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.\n\nStudy Hypothesis\n\nThe 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.\n\nStudy Design Overview\n\nRESCUE 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.\n\nKey Methodological Considerations\n\nHR-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.\n\nTemporal 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.\n\nEarly 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.\n\nSignificance\n\nRESCUE 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.",[48,55],{"label":49,"type":50,"description":51,"interventionNames":52},"Experimental: Statin + PCSK9 Inhibitor","EXPERIMENTAL","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.",[53,54],"Drug: Intervention 1","Drug: Intervention 2",{"label":56,"type":57,"description":58,"interventionNames":59},"Active Comparator: Statin Monotherapy","ACTIVE_COMPARATOR","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.",[60,61],"Drug: Intervention 3","Drug: Intervention 4",[63,70,76,80],{"type":64,"name":65,"description":66,"armGroupLabels":67,"otherNames":68},"DRUG","Intervention 1","Evolocumab Description: 140 mg subcutaneous injection every 2 weeks. Dose may be adjusted based on LDL-C response per clinical judgment.",[49],[69],"Repatha",{"type":64,"name":71,"description":72,"armGroupLabels":73,"otherNames":74},"Intervention 3","Atorvastatin Description: 20 mg orally once daily. Dose titrated to achieve LDL-C target per guidelines.",[56],[75],"Lipitor",{"type":64,"name":77,"description":78,"armGroupLabels":79,"otherNames":40},"Intervention 2","Alirocumab Description: 75 mg subcutaneous injection every 2 weeks. Dose may be adjusted based on LDL-C response per clinical judgment.",[49],{"type":64,"name":81,"description":82,"armGroupLabels":83,"otherNames":40},"Intervention 4","Rosuvastatin Description: 10 mg orally once daily. Dose titrated to achieve LDL-C target per guidelines.",[56],[85],{"name":86,"affiliation":5,"role":87},"keqiang Zhao, MD, PhD","PRINCIPAL_INVESTIGATOR",[89],{"name":90,"role":91,"phone":92,"phoneExt":40,"email":93},"keqiang Zhao, M.D.","CONTACT","0086-13810917596","zkqiang@btch.edu.cn",{"type":95,"investigatorFullName":96,"investigatorTitle":97,"investigatorAffiliation":5,"oldNameTitle":40,"oldOrganization":40},"SPONSOR_INVESTIGATOR","Keqiang Zhao","Deputy Chief Physician, Department of Vascular Surgery, Beijing Tsinghua Chang Gung Hospital","100656106","phase-4-rescue-pcsk9-inhibitors-for-carotid-vulnerable-plaque-remodeling-100656106",false,"NCT07819643","RESCUE: PCSK9 Inhibitors for Carotid Vulnerable Plaque Remodeling","Remodeling Evaluation and Stabilization of Carotid Vulnerable Plaques by PCSK9 Inhibitors Using HR-MRI for Early Prediction","RESCUE","Inclusion Criteria:\n\n1. . 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 \\\u003C0.5 mm; lipid-rich necrotic core \\[LRNC\\] volume ≥40% of plaque volume; intraplaque hemorrhage \\[IPH\\]; or neovascularization).\n2. Receiving standard statin therapy (moderate intensity or higher) for ≥3 months, with LDL-C still ≥1.8 mmol\u002FL (70 mg\u002FdL).\n3. Willing to adhere to follow-up and provide signed informed consent.\n\nExclusion Criteria:\n\n1. Allergy or contraindication to PCSK9 inhibitors.\n2. Active liver disease, myopathy, or creatine kinase (CK) elevation \\>5 times the upper limit of normal.\n3. History of carotid revascularization (carotid endarterectomy \\[CEA\\] or carotid artery stenting \\[CAS\\]).\n4. Renal insufficiency (estimated glomerular filtration rate \\[eGFR\\] \\\u003C30 ml\u002Fmin).\n5. MRI contraindications such as metallic implants or claustrophobia.\n6. Life expectancy \\\u003C3 years.","ALL","40 Years","80 Years",{"count":110,"type":111},120,"ESTIMATED","INTERVENTIONAL",[114],"PHASE4","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.\n\nHigh-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.\n\nPCSK9 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.\n\nThis 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.\n\nPurpose: 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.\n\nDesign: 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.\n\nPrimary Outcome: Change in lipid-rich necrotic core volume by HR-MRI at 12 and 24 months.\n\nSecondary Outcomes: Fibrous cap thickness, intraplaque hemorrhage, remodeling index, LDL-C levels, inflammatory markers, and clinical events (stroke, TIA, cardiovascular death) over 24 months.\n\nStatus: Not yet recruiting. Planned start: January 2027. Conducted at Beijing Tsinghua Chang Gung Hospital, Beijing, China.",[117,118,119,120],"Atherosclerosis Cerebral","Carotid Plaque","Vulnerable Plaque","Carotid Stenosis",[122,123,124,125,126,127,128],"PCSK9 inhibitor","HR-MRI","Carotid plaque","Vulnerable plaque","Plaque remodeling","Plaque stabilization","Stroke prevention","NOT_YET_RECRUITING","2026-09-13",{"date":132,"type":133},"2026-09-15","ACTUAL",{"date":135,"type":111},"2027-01-01",{"date":137,"type":111},"2029-12-01",{"name":96,"class":6}]