A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy (SLICE-CEA)
Primary Purpose
Carotid Artery Stenosis, Asymptomatic Carotid Artery Stenosis
Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Evolocumab
Sponsored by
About this trial
This is an interventional treatment trial for Carotid Artery Stenosis focused on measuring CEA, Carotid EndArterectomy, Evolocumab, Carotid Artery
Eligibility Criteria
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:
1. Evidence of IPH on MRI
Sites / Locations
- North York Diagnostic and Cardiac CentreRecruiting
- East Toronto Vascular ClinicRecruiting
- St. Michael's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Drug (Evolocumab)
No Drug (Standard of Care)
Arm Description
Individuals randomized to this arm will administer Evolocumab subcutaneously (SC) every two weeks (Q2W) for 26 weeks.
Individuals randomized to this arm will not administer a placebo.
Outcomes
Primary Outcome Measures
Change in lipid rich necrotic core (LRNC) volume
As measured by MRI
Secondary Outcome Measures
Change in vessel wall volume
As measured by MRI
Change in vessel lumen volume
As measured by MRI
Full Information
NCT ID
NCT04539223
First Posted
August 30, 2020
Last Updated
April 29, 2022
Sponsor
Canadian Medical and Surgical Knowledge Translation Research Group
Collaborators
Amgen
1. Study Identification
Unique Protocol Identification Number
NCT04539223
Brief Title
A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 28, 2020 (Actual)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
May 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Canadian Medical and Surgical Knowledge Translation Research Group
Collaborators
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carotid Artery Stenosis, Asymptomatic Carotid Artery Stenosis
Keywords
CEA, Carotid EndArterectomy, Evolocumab, Carotid Artery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Twenty-six week treatment with or without evolocumab in addition to current medical management.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Drug (Evolocumab)
Arm Type
Active Comparator
Arm Description
Individuals randomized to this arm will administer Evolocumab subcutaneously (SC) every two weeks (Q2W) for 26 weeks.
Arm Title
No Drug (Standard of Care)
Arm Type
No Intervention
Arm Description
Individuals randomized to this arm will not administer a placebo.
Intervention Type
Drug
Intervention Name(s)
Evolocumab
Intervention Description
Autoinjector 1-mL deliverable volume of 140 mg/mL
Primary Outcome Measure Information:
Title
Change in lipid rich necrotic core (LRNC) volume
Description
As measured by MRI
Time Frame
Baseline to end of treatment (average of 6 months)
Secondary Outcome Measure Information:
Title
Change in vessel wall volume
Description
As measured by MRI
Time Frame
Baseline to end of treatment (average of 6 months)
Title
Change in vessel lumen volume
Description
As measured by MRI
Time Frame
Baseline to end of treatment (average of 6 months)
Other Pre-specified Outcome Measures:
Title
Plaque Histology and Morphology
Description
Obtained at time of CEA
Time Frame
At the end of treatment (average of 6 months)
Title
Lipid Levels
Description
Serum lipid levels
Time Frame
Baseline to end of treatment (average of 6 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
1. Evidence of IPH on MRI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicole Cooke
Phone
(416) 864-6060
Ext
43932
Email
Nicole.Cooke@unityhealth.to
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohammed Al-Omran, MD
Organizational Affiliation
Unity Health Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
North York Diagnostic and Cardiac Centre
City
North York
State/Province
Ontario
ZIP/Postal Code
M6B 3H7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohammed Al-Omran
Email
Mohammed.Al-Omran@unityhealth.to
First Name & Middle Initial & Last Name & Degree
Mohammed Al-Omran
Facility Name
East Toronto Vascular Clinic
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4L3Y3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leslie Summers deLuca, PhD
Phone
416-480-6100
Ext
2593
Email
leslie.summersdeluca@sunnybrook.ca
First Name & Middle Initial & Last Name & Degree
Ahmed Kayssi, MD
First Name & Middle Initial & Last Name & Degree
Andrew Dueck, MD
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanjay Yagnik
Phone
416 864 6060
Ext
2920
Email
Sanjay.Yagnik@unityhealth.to
12. IPD Sharing Statement
Learn more about this trial
A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy
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