此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

Alirocumab for Stabilisation of Symptomatic Vulnerable Carotid Plaque (CAROTID-STABIL)

2026年5月8日 更新者：Ossama Mansour、Middle East North Africa Stroke and Interventional Neurotherapies Organization

Alirocumab for Stabilisation of Symptomatic Vulnerable Carotid Plaque: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial With High-Resolution Vessel-Wall MRI and Clinical Endpoints

CAROTID-STABILISE is a phase III, multicentre, randomised, double-blind, placebo-controlled trial evaluating whether alirocumab 150 mg subcutaneously every 2 weeks, added to high-intensity statin therapy, produces greater reduction in intraplaque haemorrhage (IPH) volume at 26 weeks compared with placebo in patients with recently symptomatic carotid stenosis of 50-69% harbouring IPH or lipid-rich necrotic core (LRNC) on high-resolution vessel-wall MRI. The study will enroll 280 participants across multiple centres with a 52-week extension for durability and clinical endpoints assessment.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

BACKGROUND: Symptomatic carotid stenosis of 50-69% carries a 30-day recurrent-stroke risk of 5-8% and a 2-year risk of 15-20% on best medical therapy alone. A substantial proportion of patients are either surgically deferred or anatomically borderline where revascularisation benefit is debated. PCSK9 inhibitors have demonstrated carotid plaque regression, reduction in lipid-rich necrotic core, and reduction in arterial inflammation. However, no RCT has tested whether PCSK9 inhibition can reduce intraplaque haemorrhage or LRNC in symptomatic carotid plaque.

DESIGN: This is a phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group superiority trial with a 26-week primary endpoint assessment and a 52-week extension. Patients with recently symptomatic carotid stenosis (50-69%) with MRI-confirmed vulnerable plaque features (IPH or LRNC) will be randomised 1:1 to alirocumab 150 mg SC q2w or matched placebo, both on background high-intensity statin therapy.

PRIMARY ENDPOINT: Absolute change in IPH volume (mm³) from baseline to week 26, measured on MPRAGE sequences by a blinded central imaging core lab using semi-automated segmentation.

SECONDARY ENDPOINTS: Include percent change in LRNC volume, absolute change in minimum fibrous cap thickness, percent change in total plaque wall volume at weeks 26 and 52, composite of ipsilateral recurrent stroke or TIA through week 52, and proportion avoiding carotid revascularisation through week 52.

SAFETY: Monitored by an independent Data and Safety Monitoring Board (DSMB) with pre-specified interim analyses at 50% and 75% enrolment.

研究类型

介入性

注册 (估计的)

280

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 卡塔尔
      • Doha、卡塔尔
        • Weill Cornell Medicine-Qatar
  • 土耳其（türkiye）
      • Eskişehir、土耳其（türkiye）
        • Department of Neurology, Eskisehir Osmangazi University
      • Istanbul、土耳其（türkiye）
        • Neurology Department, Dr. Lutfi Kirdar City Hospital
  • 埃及
      • Alexandria、埃及
        • Alexandria University, Smouha University Comprehensive Stroke Center
      • Cairo、埃及
        • Cairo University
      • Cairo、埃及
        • Ain Shams University
      • Cairo、埃及
        • Neurology Department, Al-Azhar University
  • 巴基斯坦
      • Karachi、巴基斯坦
        • Aga Khan University
  • 摩洛哥
      • Rabat、摩洛哥
        • Centre Hospitalier Universitaire Ibn Sina de Rabat
  • 沙特阿拉伯
      • Abhā、沙特阿拉伯
        • King Khalid University
      • Jeddah、沙特阿拉伯
        • King Abdulaziz Medical City
      • Mecca、沙特阿拉伯
        • King Abdullah Medical City
  • 突尼斯
      • Tunis、突尼斯
        • Institut National de Neurologie
  • 约旦
      • Amman、约旦
        • Amman Specialized IR Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. Age ≥ 40 and ≤ 80 years
  2. Recently symptomatic (TIA, amaurosis fugax, or non-disabling ischaemic stroke with mRS ≤ 2) referable to a carotid territory within 28 days of randomisation
  3. Ipsilateral extracranial internal carotid artery stenosis of 50-69% by NASCET criteria on CTA or DSA
  4. HR-VW-MRI evidence of IPH (MPRAGE hyperintensity ≥150% of adjacent sternocleidomastoid) OR LRNC ≥ 10% of plaque volume in the symptomatic plaque
  5. On a stable dose of high-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) for ≥ 4 weeks, or able and willing to initiate atorvastatin 80 mg daily at randomisation
  6. LDL-C ≥ 70 mg/dL (1.8 mmol/L) at screening
  7. Able to undergo 3T MRI (no contraindications)
  8. Provides written informed consent

Exclusion Criteria:

  1. Indication for urgent carotid revascularisation within 14 days per treating team
  2. Disabling stroke (mRS > 2) or NIHSS > 5 at randomisation
  3. Carotid stenosis ≥ 70% or occlusion
  4. Cardioembolic stroke source (atrial fibrillation, LV thrombus, endocarditis, PFO with high-risk features)
  5. Intracranial haemorrhage within 12 months or any history of symptomatic ICH
  6. eGFR < 30 mL/min/1.73 m²
  7. Active hepatobiliary disease or ALT/AST > 3x ULN
  8. Prior exposure to any PCSK9 inhibitor or inclisiran within 6 months
  9. Known hypersensitivity to alirocumab or excipients
  10. Pregnancy, breastfeeding, or unwillingness to use contraception in women of childbearing potential
  11. Life expectancy < 24 months
  12. Participation in another interventional trial within 30 days
  13. Inability to comply with follow-up or MRI schedule

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：三倍

武器和干预

参与者组/臂
干预/治疗
实验性的：Alirocumab + High-Intensity Statin
Alirocumab 150 mg subcutaneous injection every 2 weeks via pre-filled pen, self-administered or caregiver-administered, from randomisation through week 52. Plus atorvastatin 80 mg daily (or rosuvastatin 40 mg if intolerant) as background therapy.
药品：Alirocumab
Alirocumab 150 mg subcutaneous injection every 2 weeks via pre-filled pen for 52 weeks. First dose given at randomisation visit under supervision. Self-administered or caregiver-administered at home for subsequent doses. Alirocumab is a fully human monoclonal antibody that inhibits PCSK9, leading to significant LDL-C reduction beyond that achieved with statins alone.
药品：Placebo
Matched placebo subcutaneous injection every 2 weeks via pre-filled pen for 52 weeks. Visually identical to alirocumab injection. First dose given at randomisation visit under supervision. Self-administered or caregiver-administered at home for subsequent doses.
药品：Atorvastatin
Atorvastatin 80 mg oral tablet once daily as background high-intensity statin therapy for both arms. Rosuvastatin 40 mg daily may be substituted if patient is intolerant to atorvastatin. Administered throughout the entire study duration (52 weeks).
安慰剂比较：Placebo + High-Intensity Statin
Matched placebo subcutaneous injection every 2 weeks via pre-filled pen from randomisation through week 52, visually identical to alirocumab. Plus atorvastatin 80 mg daily (or rosuvastatin 40 mg if intolerant) as background therapy.
药品：Alirocumab
Alirocumab 150 mg subcutaneous injection every 2 weeks via pre-filled pen for 52 weeks. First dose given at randomisation visit under supervision. Self-administered or caregiver-administered at home for subsequent doses. Alirocumab is a fully human monoclonal antibody that inhibits PCSK9, leading to significant LDL-C reduction beyond that achieved with statins alone.
药品：Placebo
Matched placebo subcutaneous injection every 2 weeks via pre-filled pen for 52 weeks. Visually identical to alirocumab injection. First dose given at randomisation visit under supervision. Self-administered or caregiver-administered at home for subsequent doses.
药品：Atorvastatin
Atorvastatin 80 mg oral tablet once daily as background high-intensity statin therapy for both arms. Rosuvastatin 40 mg daily may be substituted if patient is intolerant to atorvastatin. Administered throughout the entire study duration (52 weeks).

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Absolute change in intraplaque haemorrhage (IPH) volume from baseline to week 26
大体时间：Baseline to 26 weeks
Absolute change in intraplaque haemorrhage volume (mm³) from baseline to week 26, measured on MPRAGE sequences by a blinded central imaging core laboratory using semi-automated segmentation. IPH is defined as hyperintensity ≥150% of adjacent sternocleidomastoid muscle signal on 3T MRI.
Baseline to 26 weeks

次要结果测量

结果测量
措施说明
大体时间
Percent change in lipid-rich necrotic core (LRNC) volume at week 26
大体时间：Baseline to 26 weeks
Percent change in lipid-rich necrotic core volume from baseline to week 26, measured on high-resolution vessel-wall MRI by a blinded central imaging core laboratory.
Baseline to 26 weeks
Absolute change in minimum fibrous cap thickness at week 26
大体时间：Baseline to 26 weeks
Absolute change in minimum fibrous cap thickness (mm) from baseline to week 26, measured on post-contrast T1 black-blood MRI by a blinded central imaging core laboratory.
Baseline to 26 weeks
Percent change in total plaque wall volume at week 26
大体时间：Baseline to 26 weeks
Percent change in total plaque wall volume (outer wall area minus lumen area summed across all slices) from baseline to week 26, measured on high-resolution vessel-wall MRI by a blinded central imaging core laboratory.
Baseline to 26 weeks
Percent change in intraplaque haemorrhage (IPH) volume at week 52
大体时间：Baseline to 52 weeks
Percent change in intraplaque haemorrhage volume from baseline to week 52, measured on MPRAGE sequences by a blinded central imaging core laboratory.
Baseline to 52 weeks
Percent change in lipid-rich necrotic core (LRNC) volume at week 52
大体时间：Baseline to 52 weeks
Percent change in lipid-rich necrotic core volume from baseline to week 52, measured on high-resolution vessel-wall MRI by a blinded central imaging core laboratory.
Baseline to 52 weeks
Composite of ipsilateral recurrent ischaemic stroke or TIA through week 52
大体时间：Randomisation to 52 weeks
Time to first occurrence of ipsilateral recurrent ischaemic stroke or transient ischaemic attack (TIA) from randomisation through week 52, adjudicated by an independent blinded clinical events committee.
Randomisation to 52 weeks
Proportion of patients avoiding carotid revascularisation through week 52
大体时间：Randomisation to 52 weeks
Proportion of patients who do not undergo carotid revascularisation (carotid endarterectomy or carotid artery stenting) through 52 weeks from randomisation, adjudicated by an independent blinded clinical events committee.
Randomisation to 52 weeks

其他结果措施

结果测量
措施说明
大体时间
Safety and tolerability composite
大体时间：Randomisation to 52 weeks
Composite safety endpoint including: serious adverse events, adverse events leading to discontinuation, injection-site reactions, new-onset diabetes, neurocognitive adverse events, frequency of LDL-C < 15 mg/dL and clinical correlates, haemorrhagic stroke, and major bleeding (BARC >= 3). Monitored continuously through 52 weeks.
Randomisation to 52 weeks

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Middle East North Africa Stroke and Interventional Neurotherapies Organization

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2027年7月1日

初级完成 (估计的)

2030年3月1日

研究完成 (估计的)

2030年9月1日

研究注册日期

首次提交

2026年5月8日

首先提交符合 QC 标准的

2026年5月8日

首次发布 (实际的)

2026年5月14日

研究记录更新

最后更新发布 (实际的)

2026年5月14日

上次提交的符合 QC 标准的更新

2026年5月8日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • MENASINO-CAROTID-2026-01

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅