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

NCT04539223 | Unknown Phase 4

• 1 other identifier: SLICE-CEA-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

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.

Conditions

Carotid Artery Stenosis; Asymptomatic Carotid Artery Stenosis

Keywords

CEA; Carotid EndArterectomy; Evolocumab; Carotid Artery

Outcome Measures

Primary Outcomes (1)

• Change in lipid rich necrotic core (LRNC) volume

  As measured by MRI

  Baseline to end of treatment (average of 6 months)

Secondary Outcomes (2)

• Change in vessel wall volume

  Baseline to end of treatment (average of 6 months)

• Change in vessel lumen volume

  Baseline to end of treatment (average of 6 months)

Other Outcomes (2)

• Plaque Histology and Morphology

  At the end of treatment (average of 6 months)

• Lipid Levels

  Baseline to end of treatment (average of 6 months)

Study Arms (2)

Drug (Evolocumab)

ACTIVE COMPARATOR

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

Drug: Evolocumab

No Drug (Standard of Care)

NO INTERVENTION

Individuals randomized to this arm will not administer a placebo.

Interventions

Evolocumab DRUG

Autoinjector 1-mL deliverable volume of 140 mg/mL

Drug (Evolocumab)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• \. Evidence of IPH on MRI

Sponsors & Collaborators

• Canadian Medical and Surgical Knowledge Translation Research Group: lead
• Amgen: collaborator

Study Sites (3)

North York Diagnostic and Cardiac Centre

North York, Ontario, M6B 3H7, Canada

RECRUITING

East Toronto Vascular Clinic

Toronto, Ontario, M4L3Y3, Canada

RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Carotid Stenosis

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Mohammed Al-Omran, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole Cooke

CONTACT

(416) 864-6060; Nicole.Cooke@unityhealth.to

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: August 30, 2020
• First Posted: September 4, 2020
• Study Start: August 28, 2020
• Primary Completion: April 1, 2022
• Study Completion: May 1, 2022
• Last Updated: May 2, 2022

Record last verified: 2022-04

Locations

CA (3)