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出境医 / 临床实验 / Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1) (EVOCAR-1)
Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1) (EVOCAR-1)
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 |
|---|---|---|
| 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.
Study Design
| 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 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Placebo Comparator: Placebo
Matching Placebo.
|
Drug: Placebo Auto-Injector
Matching Placebo for the active comparator (Evolocumab)
Other Name: Placebo
|
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Active Comparator: Evolocumab
Evolocumab Auto-Injector [Repatha]
|
Drug: Evolocumab Auto-Injector [Repatha]
Auto-Injector, 140 mg every two weeks.
Other Name: Repatha
|
Outcome Measures
Primary Outcome Measures :
- 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 :
- Percentage of LRNC core [ Time Frame: 12 months ]Change in percentage lipid-rich necrotic core (LRNC) at 12 months, compared to baseline
- LRNC regression [ Time Frame: 12 months ]Percentage of participants achieving LRNC regression at 12 months
- LRNC volume [ Time Frame: 24 months ]Change in carotid plaque LRNC volume at other time-points, compared to baseline
- LRNC percentage [ Time Frame: 24 months ]Change in carotid plaque LRNC percentage at other time-points, compared to baseline
- Measures of other carotid plaque burden - Volume wall thickness [ Time Frame: 24 months ]Absolute and percentage change, compared to baseline, of volume wall thickness
- Measures of other carotid plaque burden - Volume wall area [ Time Frame: 24 months ]Absolute and percentage change, compared to baseline, volume wall area
- Measures of other carotid plaque burden - Calcification [ Time Frame: 24 months ]Absolute and percentage change, compared to baseline, of plaque composition (calcification)
- 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)
- 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:
- Exploratory outcomes 1: Change in biochemical parameters - total cholesterol [ Time Frame: 24 months ]Absolute and percentage change compared to baseline in total cholesterol.
- Exploratory outcomes 1: Change in biochemical parameters - LDL-C [ Time Frame: 24 months ]Absolute and percentage change compared to baseline in LDL-C.
- 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).
- Exploratory outcomes 1: Change in biochemical parameters - triglycerides [ Time Frame: 24 months ]Absolute and percentage change compared to baseline in triglycerides.
- Exploratory outcomes 1: Change in biochemical parameters - lipoprotein (a) [ Time Frame: 24 months ]Absolute and percentage change compared to baseline in lipoprotein(a).
- 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
- 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
- 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
- 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
- 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
- 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
- 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,
Eligibility Criteria
| 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
Contacts and Locations
Contacts
| Contact: Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD | +44 20 3313 3405 | j.cegla@imperial.ac.uk |
Locations
| 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
| Principal Investigator: | Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD | Imperial College London |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 15, 2019 | ||||||
| First Posted Date ICMJE | April 30, 2019 | ||||||
| Last Update Posted Date | December 10, 2020 | ||||||
| Actual Study Start Date ICMJE | September 4, 2019 | ||||||
| Estimated Primary Completion Date | September 4, 2023 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
Change in lipid-rich necrotic core [ Time Frame: 12 months ] Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||
| Change History | |||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures |
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| Original Other Pre-specified Outcome Measures |
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| Descriptive Information | |||||||
| Brief Title ICMJE | Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1) | ||||||
| Official Title ICMJE | Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis | ||||||
| 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. |
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| Study Type ICMJE | Interventional | ||||||
| Study Phase ICMJE | Phase 4 | ||||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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| Condition ICMJE | Carotid Artery Stenosis | ||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||
| Recruitment Status ICMJE | Recruiting | ||||||
| Estimated Enrollment ICMJE |
60 | ||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||
| Estimated Study Completion Date ICMJE | September 4, 2023 | ||||||
| Estimated Primary Completion Date | September 4, 2023 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | United Kingdom | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT03931161 | ||||||
| Other Study ID Numbers ICMJE | EVOCAR-1 | ||||||
| Has Data Monitoring Committee | Yes | ||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Imperial College Healthcare NHS Trust | ||||||
| Study Sponsor ICMJE | Imperial College Healthcare NHS Trust | ||||||
| Collaborators ICMJE | Imperial College London | ||||||
| Investigators ICMJE |
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| PRS Account | Imperial College Healthcare NHS Trust | ||||||
| Verification Date | December 2020 | ||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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