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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Carotid Artery Stenosis; Asymptomatic Carotid Artery Stenosis
• Intervention / Treatment: Drug: Evolocumab

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nicole Cooke; Phone Number: 43932 (416) 864-6060; Email: Nicole.Cooke@unityhealth.to

Study Locations

• Canada
  • Ontario
    • North York, Ontario, Canada, M6B 3H7
      • Recruiting
      • North York Diagnostic and Cardiac Centre
      • Contact: Mohammed Al-Omran; Email: Mohammed.Al-Omran@unityhealth.to
      • Principal Investigator: Mohammed Al-Omran
    • Toronto, Ontario, Canada
      • Recruiting
      • St. Michael's Hospital
      • Contact: Sanjay Yagnik; Phone Number: 2920 416 864 6060; Email: Sanjay.Yagnik@unityhealth.to
    • Toronto, Ontario, Canada, M4L3Y3
      • Recruiting
      • East Toronto Vascular Clinic
      • Principal Investigator: Ahmed Kayssi, MD
      • Contact: Leslie Summers deLuca, PhD; Phone Number: 2593 416-480-6100; Email: leslie.summersdeluca@sunnybrook.ca
      • Sub-Investigator: Andrew Dueck, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plaque Histology and Morphology	Obtained at time of CEA	At the end of treatment (average of 6 months)
Lipid Levels	Serum lipid levels	Baseline to end of treatment (average of 6 months)

Collaborators and Investigators

• Sponsor: Canadian Medical and Surgical Knowledge Translation Research Group
• Collaborators: Amgen
• Investigators: Principal Investigator: Mohammed Al-Omran, MD, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: August 30, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (Actual): September 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: CEA; Evolocumab; Carotid Artery; Carotid EndArterectomy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Carotid Artery Diseases; Carotid Stenosis; Constriction, Pathologic; Plaque, Atherosclerotic; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: SLICE-CEA-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No