A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy

Carotid Artery Stenosis Clinical Trial

— SLICE-CEA  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04539223
• Other study ID #: SLICE-CEA-001
• Status: Recruiting
• Phase: Phase 4
• Start date: August 28, 2020
• Est. completion date: May 2022

Study information

• Verified date: April 2022
• Source: Canadian Medical and Surgical Knowledge Translation Research Group
• Contact: Nicole Cooke
• Phone: (416) 864-6060
• Email: Nicole.Cooke[@]unityhealth.to
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asymptomatic Carotid Artery Stenosis
• Carotid Artery Stenosis
• Carotid Stenosis
• Constriction, Pathologic
• Plaque, Atherosclerotic

Intervention

Drug:
• Evolocumab
Autoinjector 1-mL deliverable volume of 140 mg/mL

Locations

Country	Name	City	State
Canada	North York Diagnostic and Cardiac Centre	North York	Ontario
Canada	East Toronto Vascular Clinic	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Canadian Medical and Surgical Knowledge Translation Research Group	Amgen

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plaque Histology and Morphology	Obtained at time of CEA	At the end of treatment (average of 6 months)
Other	Lipid Levels	Serum lipid levels	Baseline to end of treatment (average of 6 months)
Primary	Change in lipid rich necrotic core (LRNC) volume	As measured by MRI	Baseline to end of treatment (average of 6 months)
Secondary	Change in vessel wall volume	As measured by MRI	Baseline to end of treatment (average of 6 months)
Secondary	Change in vessel lumen volume	As measured by MRI	Baseline to end of treatment (average of 6 months)