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

Sponsor

Canadian Medical and Surgical Knowledge Translation Research Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT04539223

Collaborator

Amgen (Industry)

Enrollment

Locations

Arms

20.1

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carotid Artery Stenosis Asymptomatic Carotid Artery Stenosis	Drug: Evolocumab	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Twenty-six week treatment with or without evolocumab in addition to current medical management.Twenty-six week treatment with or without evolocumab in addition to current medical management.

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 28, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Drug (Evolocumab)

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

Drug: Evolocumab

Autoinjector 1-mL deliverable volume of 140 mg/mL

No Intervention: No Drug (Standard of Care)

Individuals randomized to this arm will not administer a placebo.

Outcome Measures

Primary Outcome Measures

Change in lipid rich necrotic core (LRNC) volume [Baseline to end of treatment (average of 6 months)]
As measured by MRI

Secondary Outcome Measures

Change in vessel wall volume [Baseline to end of treatment (average of 6 months)]
As measured by MRI
Change in vessel lumen volume [Baseline to end of treatment (average of 6 months)]
As measured by MRI

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Evidence of IPH on MRI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North York Diagnostic and Cardiac Centre	North York	Ontario	Canada	M6B 3H7
2	East Toronto Vascular Clinic	Toronto	Ontario	Canada	M4L3Y3
3	St. Michael's Hospital	Toronto	Ontario	Canada