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

Sponsor
Imperial College Healthcare NHS Trust (Other)
Overall Status
Recruiting
CT.gov ID
NCT03931161
Collaborator
Imperial College London (Other)
60
1
2
48
1.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Evolocumab Auto-Injector [Repatha]
  • Drug: Placebo Auto-Injector
Phase 4

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis
Actual Study Start Date :
Sep 4, 2019
Anticipated Primary Completion Date :
Sep 4, 2023
Anticipated Study Completion Date :
Sep 4, 2023

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Matching Placebo.

Drug: Placebo Auto-Injector
Matching Placebo for the active comparator (Evolocumab)
Other Names:
  • Placebo
  • Active Comparator: Evolocumab

    Evolocumab Auto-Injector [Repatha]

    Drug: Evolocumab Auto-Injector [Repatha]
    Auto-Injector, 140 mg every two weeks.
    Other Names:
  • Repatha
  • Outcome Measures

    Primary Outcome Measures

    1. Change in lipid-rich necrotic core [12 months]

      Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline

    Secondary Outcome Measures

    1. Percentage of LRNC core [12 months]

      Change in percentage lipid-rich necrotic core (LRNC) at 12 months, compared to baseline

    2. LRNC regression [12 months]

      Percentage of participants achieving LRNC regression at 12 months

    3. LRNC volume [24 months]

      Change in carotid plaque LRNC volume at other time-points, compared to baseline

    4. LRNC percentage [24 months]

      Change in carotid plaque LRNC percentage at other time-points, compared to baseline

    5. Measures of other carotid plaque burden - Volume wall thickness [24 months]

      Absolute and percentage change, compared to baseline, of volume wall thickness

    6. Measures of other carotid plaque burden - Volume wall area [24 months]

      Absolute and percentage change, compared to baseline, volume wall area

    7. Measures of other carotid plaque burden - Calcification [24 months]

      Absolute and percentage change, compared to baseline, of plaque composition (calcification)

    8. Measures of other carotid plaque burden - Fibrous tissue volume [24 months]

      Absolute and percentage change, compared to baseline, of plaque composition (fibrous tissue volume)

    9. Measures of other carotid plaque burden - New intra-plaque haemorrhage [24 months]

      Absolute and percentage change, compared to baseline, of plaque composition (new intra-plaque haemorrhage)

    Other Outcome Measures

    1. Exploratory outcomes 1: Change in biochemical parameters - total cholesterol [24 months]

      Absolute and percentage change compared to baseline in total cholesterol.

    2. Exploratory outcomes 1: Change in biochemical parameters - LDL-C [24 months]

      Absolute and percentage change compared to baseline in LDL-C.

    3. Exploratory outcomes 1: Change in biochemical parameters - HDL-C [24 months]

      Absolute and percentage change compared to baseline in high density lipoprotein-associated cholesterol (HDL-C).

    4. Exploratory outcomes 1: Change in biochemical parameters - triglycerides [24 months]

      Absolute and percentage change compared to baseline in triglycerides.

    5. Exploratory outcomes 1: Change in biochemical parameters - lipoprotein (a) [24 months]

      Absolute and percentage change compared to baseline in lipoprotein(a).

    6. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Ischaemic and non-ischaemic stroke [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Ischaemic and non-ischaemic stroke

    7. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - TIA [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Transient ischaemic attack

    8. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Progression to carotid endarterectomy [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Progression to carotid endarterectomy

    9. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - MI [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Myocardial infarction

    10. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Unstable angina [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Unstable angina

    11. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events - Hospitalisation for heart failure [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: Hospitalisation for heart failure

    12. Exploratory outcomes 2: Number of patients with Cardio & cerebrovascular events -PAD-related end points: peripheral revascularization, [24 months]

      Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: PAD-related end points: peripheral revascularization,

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Imperial College Healthcare NHS Trust London United Kingdom W12 0HS

    Sponsors and Collaborators

    • Imperial College Healthcare NHS Trust
    • Imperial College London

    Investigators

    • Principal Investigator: Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD, Imperial College London

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Imperial College Healthcare NHS Trust
    ClinicalTrials.gov Identifier:
    NCT03931161
    Other Study ID Numbers:
    • EVOCAR-1
    First Posted:
    Apr 30, 2019
    Last Update Posted:
    Sep 8, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Imperial College Healthcare NHS Trust
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 8, 2021