Clinical trial NCT04539223: A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Carotid Artery Stenosis
Asymptomatic Carotid Artery Stenosis
Keywords: CEA
Carotid EndArterectomy
Evolocumab
Carotid Artery
Lead sponsor: Canadian Medical and Surgical Knowledge Translation Research Group
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2020-09-04
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Twenty-six week treatment with or without evolocumab in addition to current medical management.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in lipid rich necrotic core (LRNC) volume
timeFrame: Baseline to end of treatment (average of 6 months)
Secondary outcomes:
measure: Change in vessel wall volume
timeFrame: Baseline to end of treatment (average of 6 months)
measure: Change in vessel lumen volume
timeFrame: Baseline to end of treatment (average of 6 months)
Other outcomes:
measure: Plaque Histology and Morphology
timeFrame: At the end of treatment (average of 6 months)
measure: Lipid Levels
timeFrame: Baseline to end of treatment (average of 6 months)
Locations:
city: North York
country: Canada
facility: North York Diagnostic and Cardiac Centre
state: Ontario
city: Toronto
country: Canada
facility: East Toronto Vascular Clinic
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Mohammed Al-Omran, MD
role: PRINCIPAL_INVESTIGATOR
References: