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Trial record 8 of 113 for:    Recruiting, Not yet recruiting, Available Studies | Common carotid artery

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

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ClinicalTrials.gov Identifier: NCT03931161
Recruitment Status : Recruiting
First Posted : April 30, 2019
Last Update Posted : September 10, 2019
Sponsor:
Collaborator:
Imperial College London
Information provided by (Responsible Party):
Imperial College Healthcare NHS Trust

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
Carotid Artery Stenosis 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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 4, 2019
Estimated Primary Completion Date : September 4, 2023
Estimated Study Completion Date : September 4, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Placebo Comparator: Placebo
Matching Placebo.
Drug: Placebo Auto-Injector
Matching Placebo for the active comparator (Evolocumab)
Other Name: Placebo

Active Comparator: Evolocumab
Evolocumab Auto-Injector [Repatha]
Drug: Evolocumab Auto-Injector [Repatha]
Auto-Injector, 140 mg every two weeks.
Other Name: Repatha




Primary Outcome Measures :
  1. Change in lipid-rich necrotic core [ Time Frame: 12 months ]
    Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline


Secondary Outcome Measures :
  1. Percentage of LRNC core [ Time Frame: 12 months ]
    Change in percentage lipid-rich necrotic core (LRNC) at 12 months, compared to baseline

  2. LRNC regression [ Time Frame: 12 months ]
    Percentage of participants achieving LRNC regression at 12 months

  3. LRNC volume [ Time Frame: 24 months ]
    Change in carotid plaque LRNC volume at other time-points, compared to baseline

  4. LRNC percentage [ Time Frame: 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 [ Time Frame: 24 months ]
    Absolute and percentage change, compared to baseline, of volume wall thickness

  6. Measures of other carotid plaque burden - Volume wall area [ Time Frame: 24 months ]
    Absolute and percentage change, compared to baseline, volume wall area

  7. Measures of other carotid plaque burden - Calcification [ Time Frame: 24 months ]
    Absolute and percentage change, compared to baseline, of plaque composition (calcification)

  8. Measures of other carotid plaque burden - Fibrous tissue volume [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 24 months ]
    Absolute and percentage change compared to baseline in total cholesterol.

  2. Exploratory outcomes 1: Change in biochemical parameters - LDL-C [ Time Frame: 24 months ]
    Absolute and percentage change compared to baseline in LDL-C.

  3. Exploratory outcomes 1: Change in biochemical parameters - HDL-C [ Time Frame: 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 [ Time Frame: 24 months ]
    Absolute and percentage change compared to baseline in triglycerides.

  5. Exploratory outcomes 1: Change in biochemical parameters - lipoprotein (a) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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, [ Time Frame: 24 months ]
    Cardio- and cerebrovascular events [be adjudicated by the Investigators], including: PAD-related end points: peripheral revascularization,



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03931161


Contacts
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Contact: Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD +44 20 3313 3405 j.cegla@imperial.ac.uk

Locations
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United Kingdom
Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom, W12 0HS
Contact: Jaimini Cegla         
Sponsors and Collaborators
Imperial College Healthcare NHS Trust
Imperial College London
Investigators
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Principal Investigator: Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD Imperial College London

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Responsible Party: Imperial College Healthcare NHS Trust
ClinicalTrials.gov Identifier: NCT03931161     History of Changes
Other Study ID Numbers: EVOCAR-1
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
carotid plaque morphology
carotid plaque composition
evolocumab
Additional relevant MeSH terms:
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Carotid Stenosis
Carotid Artery Diseases
Arterial Occlusive Diseases
Constriction, Pathologic
Pathological Conditions, Anatomical
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs