Asymptomatic Carotid Artery Stenosis, Carotid Artery Stenosis
Conditions
Keywords
CEA, Carotid EndArterectomy, Evolocumab, Carotid Artery
Brief summary
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.
Interventions
DRUGEvolocumab
Autoinjector 1-mL deliverable volume of 140 mg/mL
Sponsors
Amgen
Canadian Medical and Surgical Knowledge Translation Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Twenty-six week treatment with or without evolocumab in addition to current medical management.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 40 years old 2. Significant (70-99%) carotid artery stenosis on one side, as measured by duplex ultrasound or angiogram 3. Asymptomatic carotid stenosis (no history of ipsilateral stroke or TIA within 180 days) 4. Deemed to be fit for carotid endarterectomy 5. 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. 6. 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
1. Contraindications for MRI (pacemaker; neurostimulator; non-removable metal fragments in the eye; etc.) 2. Patients in whom additional lowering of LDL-C with evolocumab is deemed to be clinically inappropriate 3. Currently taking simvastatin \>40mg/day 4. High risk comorbidities such as severe heart failure, severe COPD, severe renal disease, known severe hepatic impairment, unstable coronary syndrome, and/or advanced dementia 5. eGFR \<30 mL/min/1.73m2 6. Current, prior within past year, or known planned use of PCSK9 inhibition treatment 7. Known intolerance or allergy to evolocumab or other PCSK9 inhibitors 8. Known latex allergy 9. Women who are pregnant or breastfeeding 10. 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 11. Inability to comply with protocol-required study visits or procedures, including administration of study drug 12. Severe concomitant disease that is expected to reduce life expectancy to less than 5 years 13. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in lipid rich necrotic core (LRNC) volume | Baseline to end of treatment (average of 6 months) | As measured by MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in vessel lumen volume | Baseline to end of treatment (average of 6 months) | As measured by MRI |
| Change in vessel wall volume | Baseline to end of treatment (average of 6 months) | As measured by MRI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plaque Histology and Morphology | At the end of treatment (average of 6 months) | Obtained at time of CEA |
| Lipid Levels | Baseline to end of treatment (average of 6 months) | Serum lipid levels |
Countries
Canada
Contacts
Primary ContactNicole Cooke
Outcome results
None listed