A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy

Study Overview
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Brief Summary
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This is a multicenter, randomized, open label study with blinded outcome assessment to evaluate the impact of additional/intensive LDL-cholesterol reduction with evolocumab on carotid artery atherosclerotic plaques in higher risk subjects with severe asymptomatic but vulnerable plaques.

Official Title
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Study of Lipids Inside the Carotid With Evolocumab: A Randomized Trial of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy (SLICE-CEA CardioLink-8 Study)

Conditions
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Carotid Artery Stenosis, Asymptomatic Carotid Artery Stenosis

Intervention / Treatment
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* Drug: Evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 40 years old Significant (70-99%) carotid artery stenosis on one side, as measured by duplex ultrasound or angiogram Asymptomatic carotid stenosis (no history of ipsilateral stroke or TIA within 180 days) Deemed to be fit for carotid endarterectomy At least one of the following high-risk features: (a) prior stroke >6months prior to randomization; (b) peripheral artery disease; (c) current smoker; (d) type 2 diabetes; (e) eGFR ≥ 30 mL/min/1.73m2 and <60 ml/min/1.73m2; (f) hsCRP > 2mg/L in the absence of alternative known causes of hsCRP elevations including autoimmune diseases or active infections. On a moderate to high intensity statin therapy (defined as atorvastatin 40-80mg daily, rosuvastatin 20-40mg or simvastatin 40mg daily) unless a lower dose, or another statin or non-statin therapy is clinically justified Exclusion Criteria: Contraindications for MRI (pacemaker; neurostimulator; non-removable metal fragments in the eye; etc.) Patients in whom additional lowering of LDL-C with evolocumab is deemed to be clinically inappropriate Currently taking simvastatin >40mg/day High risk comorbidities such as severe heart failure, severe COPD, severe renal disease, known severe hepatic impairment, unstable coronary syndrome, and/or advanced dementia eGFR <30 mL/min/1.73m2 Current, prior within past year, or known planned use of PCSK9 inhibition treatment Known intolerance or allergy to evolocumab or other PCSK9 inhibitors Known latex allergy Women who are pregnant or breastfeeding Women of child bearing potential who are unwilling to use proper family planning or birth control methods to avoid pregnancy. Women are considered post-menopausal and not of childbearing potential after 12 months of natural (spontaneous) amenorrhea or have had a surgical procedure such as hysterectomy which makes pregnancy impossible Inability to comply with protocol-required study visits or procedures, including administration of study drug Severe concomitant disease that is expected to reduce life expectancy to less than 5 years Participation in another investigational device or drug study which is likely to affect the primary outcome, within 30 days of planned initiation of study drug Additional Inclusion Criteria If all eligibility criteria listed above are met, participants with only one high risk feature will undergo a time-of-flight MR angiogram, where one additional inclusion criteria will be assessed to confirm eligibility: 1. Evidence of IPH on MRI

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Twenty-six week treatment with or without evolocumab in addition to current medical management.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drug (Evolocumab)<br>Individuals randomized to this arm will administer Evolocumab subcutaneously (SC) every two weeks (Q2W) for 26 weeks. | Drug: Evolocumab<br>* Autoinjector 1-mL deliverable volume of 140 mg/mL<br>|
| No Intervention: No Drug (Standard of Care)<br>Individuals randomized to this arm will not administer a placebo. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipid rich necrotic core (LRNC) volume | As measured by MRI | Baseline to end of treatment (average of 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vessel wall volume | As measured by MRI | Baseline to end of treatment (average of 6 months) | 
| Change in vessel lumen volume | As measured by MRI | Baseline to end of treatment (average of 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CEA, Carotid EndArterectomy, Evolocumab, Carotid Artery