Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1)

Carotid Artery Stenosis Clinical Trial

— EVOCAR-1  

Official title:

Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03931161
• Other study ID #: EVOCAR-1
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 4, 2019
• Est. completion date: May 6, 2024

Study information

• Verified date: October 2022
• Source: Imperial College Healthcare NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase IV, randomised, placebo-controlled, double-blind, parallel group study to determine the effect of Evolocumab treatment on carotid plaque morphology and composition in asymptomatic patients with >50% carotid artery stenosis.

Description:

In this study patients will be randomised in a 1:1 ratio to receive Evolocumab 140 mg every two weeks or matching placebo, to be administered for 12 months. After 12 months of treatment, patients will remain in follow-up for a further 12 months.

High resolution magnetic resonance imaging (MRI) will be used to serially monitor the impact of Evolocumab on carotid plaque morphology and composition in patients with significant carotid stenosis who do not meet clinical criteria for carotid endarterectomy. This approach will reveal if clinically beneficial plaque regression occurs, without requiring the large patient cohorts or long follow-up needed for cardiovascular outcome trials.

Results from this study will establish whether treatment with Evolocumab is likely to be beneficial to patients with asymptomatic carotid stenosis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 33
• Est. completion date: May 6, 2024
• Est. primary completion date: May 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years

• Sufficient English language ability to adequately understand the study

• Able to give informed consent

• Significant carotid artery plaque with 50-70% stenosis on ultrasound or MRI performed prior to screening

• Significant asymptomatic carotid artery plaque with >70% stenosis on ultrasound or MRI performed prior to screening, but carotid endarterectomy or carotid artery stenting has been deemed unsuitable by multidisciplinary team during routine clinical care

• Lipid-rich necrotic core (LRNC) on baseline MRI scan

• Adequate image quality for MRI analysis.

• LDL-C =2.6 mmol/L (100 mg/dL)

• On stable dose of maximally-tolerated lipid-lowering therapy in accordance with UK national clinical guidelines (NICE CG18120) for =2 months prior to screening. Acceptable non-statin lipid-lowering medications include ezetimibe or a fibrate.

Exclusion Criteria:

• Any medical condition which, in the opinion of the investigators, would present an unacceptable risk to the participant if they were to take part in the trial, or prevent them from following the trial protocol

• Current or previous treatment with a PCSK9 inhibitor

• Eligible for PCSK9 inhibitor treatment under current NICE guidelines

• Contra-indication to or inability to use Evolocumab treatment, including:

• Sensitivity to Evolocumab or any associated excipients

• Unable to tolerate or perform self-administration of Evolocumab by auto-injector

• Lack of suitable refrigerated storage

• Contra-indication to or inability to tolerate MRI

• Estimated glomerular filtration rate (eGFR) =45 mL/min/1.73 m2 prior to MRI scan

• Pregnancy or breast-feeding

• Women of childbearing potential who are unwilling or unable to use a highly effective method of contraception

Related Conditions & MeSH terms

• Carotid Artery Stenosis
• Carotid Stenosis
• Constriction, Pathologic

Intervention

Drug:
• Evolocumab Auto-Injector [Repatha]
Auto-Injector, 140 mg every two weeks.
• Placebo Auto-Injector
Matching Placebo for the active comparator (Evolocumab)

Locations

Country	Name	City	State
United Kingdom	Imperial College Healthcare NHS Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College Healthcare NHS Trust	Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcomes 1: Change in biochemical parameters - total cholesterol	Absolute and percentage change compared to baseline in total cholesterol.	24 months
Other	Exploratory outcomes 1: Change in biochemical parameters - LDL-C	Absolute and percentage change compared to baseline in LDL-C.	24 months
Other	Exploratory outcomes 1: Change in biochemical parameters - HDL-C	Absolute and percentage change compared to baseline in high density lipoprotein-associated cholesterol (HDL-C).	24 months
Other	Exploratory outcomes 1: Change in biochemical parameters - triglycerides	Absolute and percentage change compared to baseline in triglycerides.	24 months
Other	Exploratory outcomes 1: Change in biochemical parameters - lipoprotein (a)	Absolute and percentage change compared to baseline in lipoprotein(a).	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Ischaemic and non-ischaemic stroke	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Ischaemic and non-ischaemic stroke	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - TIA	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Transient ischaemic attack	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Progression to carotid endarterectomy	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Progression to carotid endarterectomy	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - MI	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Myocardial infarction	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Unstable angina	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Unstable angina	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Hospitalisation for heart failure	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Hospitalisation for heart failure	24 months
Other	Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events -PAD-related end points: peripheral revascularization,	Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: PAD-related end points: peripheral revascularization,	24 months
Primary	Change in lipid-rich necrotic core	Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline	12 months
Secondary	Percentage of LRNC core	Change in percentage lipid-rich necrotic core (LRNC) at 12 months, compared to baseline	12 months
Secondary	LRNC regression	Percentage of participants achieving LRNC regression at 12 months	12 months
Secondary	LRNC volume	Change in carotid plaque LRNC volume at other time-points, compared to baseline	24 months
Secondary	LRNC percentage	Change in carotid plaque LRNC percentage at other time-points, compared to baseline	24 months
Secondary	Measures of other carotid plaque burden - Volume wall thickness	Absolute and percentage change, compared to baseline, of volume wall thickness	24 months
Secondary	Measures of other carotid plaque burden - Volume wall area	Absolute and percentage change, compared to baseline, volume wall area	24 months
Secondary	Measures of other carotid plaque burden - Calcification	Absolute and percentage change, compared to baseline, of plaque composition (calcification)	24 months
Secondary	Measures of other carotid plaque burden - Fibrous tissue volume	Absolute and percentage change, compared to baseline, of plaque composition (fibrous tissue volume)	24 months
Secondary	Measures of other carotid plaque burden - New intra-plaque haemorrhage	Absolute and percentage change, compared to baseline, of plaque composition (new intra-plaque haemorrhage)	24 months