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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Carotid Stenosis
• Intervention / Treatment: Drug: Alirocumab; Drug: Placebo; Drug: Atorvastatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt
    • Alexandria University, Smouha University Comprehensive Stroke Center
  • Cairo, Egypt
    • Cairo University
  • Cairo, Egypt
    • Ain Shams University
  • Cairo, Egypt
    • Neurology Department, Al-Azhar University
• Jordan
  • Amman, Jordan
    • Amman Specialized IR Center
• Morocco
  • Rabat, Morocco
    • Centre Hospitalier Universitaire Ibn Sina de Rabat
• Pakistan
  • Karachi, Pakistan
    • Aga Khan University
• Qatar
  • Doha, Qatar
    • Weill Cornell Medicine-Qatar
• Saudi Arabia
  • Abhā, Saudi Arabia
    • King Khalid University
  • Jeddah, Saudi Arabia
    • King Abdulaziz Medical City
  • Mecca, Saudi Arabia
    • King Abdullah Medical City
• Tunisia
  • Tunis, Tunisia
    • Institut National de Neurologie
• Turkey (Türkiye)
  • Eskişehir, Turkey (Türkiye)
    • Department of Neurology, Eskisehir Osmangazi University
  • Istanbul, Turkey (Türkiye)
    • Neurology Department, Dr. Lutfi Kirdar City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.; Drug: 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.; Drug: 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).
Placebo Comparator: 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.	Drug: 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.; Drug: 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.; Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in intraplaque haemorrhage (IPH) volume from baseline to week 26	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in lipid-rich necrotic core (LRNC) volume at week 26	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	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	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	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	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	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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability composite	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

Collaborators and Investigators

• Sponsor: Middle East North Africa Stroke and Interventional Neurotherapies Organization

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2027
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PCSK9 inhibitor; vulnerable plaque; alirocumab
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Carotid Stenosis; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Pyrroles; Heptanoic Acids; Atorvastatin; alirocumab
• Other Study ID Numbers: MENASINO-CAROTID-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No