A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy (SLICE-CEA)

Canadian Medical and Surgical Knowledge Translation Research Group

Status and phase: Enrolling; Phase 4

Conditions: Asymptomatic Carotid Artery Stenosis; Carotid Artery Stenosis

Treatments: Drug: Evolocumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04539223

SLICE-CEA-001

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 2 patient groups

Drug (Evolocumab)

Active Comparator group

Description:

Individuals randomized to this arm will administer Evolocumab subcutaneously (SC) every two weeks (Q2W) for 26 weeks.

Treatment:

Drug: Evolocumab

No Drug (Standard of Care)

No Intervention group

Description:

Individuals randomized to this arm will not administer a placebo.