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

NCT ID: NCT03931161

Last Updated: 2022-10-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-04
• Study Completion Date: 2024-05-06

Brief 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.

Detailed 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.

Conditions

Carotid Artery Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Matching Placebo.

Group Type: PLACEBO_COMPARATOR

Placebo Auto-Injector

Intervention Type: DRUG

Matching Placebo for the active comparator (Evolocumab)

Evolocumab

Evolocumab Auto-Injector \[Repatha\]

Group Type: ACTIVE_COMPARATOR

Evolocumab Auto-Injector [Repatha]

Intervention Type: DRUG

Auto-Injector, 140 mg every two weeks.

Interventions

Evolocumab Auto-Injector [Repatha]

Auto-Injector, 140 mg every two weeks.

Intervention Type: DRUG

Placebo Auto-Injector

Matching Placebo for the active comparator (Evolocumab)

Intervention Type: DRUG

Other Intervention Names

Repatha; Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: collaborator

Imperial College Healthcare NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

EVOCAR-1

Identifier Type: -

Identifier Source: org_study_id