Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Change in lipid-rich necrotic core
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Placebo
Matching Placebo.
干预措施: Placebo Auto-Injector (Drug)
Evolocumab
Evolocumab Auto-Injector [Repatha]
干预措施: Evolocumab Auto-Injector [Repatha] (Drug)
结局指标
主要结局
Change in lipid-rich necrotic core
时间窗: 12 months
Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline
次要结局
- LRNC percentage(24 months)
- Measures of other carotid plaque burden - Volume wall thickness(24 months)
- Measures of other carotid plaque burden - Calcification(24 months)
- Measures of other carotid plaque burden - New intra-plaque haemorrhage(24 months)
- Measures of other carotid plaque burden - Volume wall area(24 months)
- Measures of other carotid plaque burden - Fibrous tissue volume(24 months)
- Percentage of LRNC core(12 months)
- LRNC regression(12 months)
- LRNC volume(24 months)