Alirocumab for Stabilisation of Symptomatic Vulnerable Carotid Plaque

NCT07586540 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: MENASINO-CAROTID-2026-01
• Study Type: interventional
• Target: 280
• Locations: 7 countries
• Sites: 13

Brief Summary

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.

Conditions

Carotid Stenosis

Keywords

vulnerable plaque; alirocumab; PCSK9 inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Percent change in lipid-rich necrotic core (LRNC) volume at week 26

  Baseline to 26 weeks

• Absolute change in minimum fibrous cap thickness at week 26

  Baseline to 26 weeks

• Percent change in total plaque wall volume at week 26

  Baseline to 26 weeks

• Percent change in intraplaque haemorrhage (IPH) volume at week 52

  Baseline to 52 weeks

• Percent change in lipid-rich necrotic core (LRNC) volume at week 52

  Baseline to 52 weeks

Other Outcomes (1)

• Safety and tolerability composite

  Randomisation to 52 weeks

Study Arms (2)

Alirocumab + High-Intensity Statin

EXPERIMENTAL

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; Drug: Placebo; Drug: Atorvastatin

Placebo + High-Intensity Statin

PLACEBO COMPARATOR

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; Drug: Placebo; Drug: Atorvastatin

Interventions

Alirocumab DRUG

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.

Alirocumab + High-Intensity Statin; Placebo + High-Intensity Statin

Placebo DRUG

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.

Alirocumab + High-Intensity Statin; Placebo + High-Intensity Statin

Atorvastatin DRUG

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).

Alirocumab + High-Intensity Statin; Placebo + High-Intensity Statin

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 40 and ≤ 80 years
• Recently symptomatic (TIA, amaurosis fugax, or non-disabling ischaemic stroke with mRS ≤ 2) referable to a carotid territory within 28 days of randomisation
• Ipsilateral extracranial internal carotid artery stenosis of 50-69% by NASCET criteria on CTA or DSA
• HR-VW-MRI evidence of IPH (MPRAGE hyperintensity ≥150% of adjacent sternocleidomastoid) OR LRNC ≥ 10% of plaque volume in the symptomatic plaque
• 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
• LDL-C ≥ 70 mg/dL (1.8 mmol/L) at screening
• Able to undergo 3T MRI (no contraindications)
• Provides written informed consent

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (14)

Alexandria University, Smouha University Comprehensive Stroke Center

Alexandria, Egypt

Location

Ain Shams University

Cairo, Egypt

Location

Cairo University

Cairo, Egypt

Location

Neurology Department, Al-Azhar University

Cairo, Egypt

Location

Amman Specialized IR Center

Amman, Jordan

Location

Centre Hospitalier Universitaire Ibn Sina de Rabat

Rabat, Morocco

Location

Aga Khan University

Karachi, Pakistan

Location

Weill Cornell Medicine-Qatar

Doha, Qatar

Location

King Khalid University

Abhā, Saudi Arabia

Location

King Abdulaziz Medical City

Jeddah, Saudi Arabia

Location

King Abdullah Medical City

Mecca, Saudi Arabia

Location

Institut National de Neurologie

Tunis, Tunisia

Location

Department of Neurology, Eskisehir Osmangazi University

Eskişehir, Turkey (Türkiye)

Location

Neurology Department, Dr. Lutfi Kirdar City Hospital

Istanbul, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Carotid Stenosis

Interventions

alirocumab; Atorvastatin

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, Alexandria University

Study Record Dates

• First Submitted: May 8, 2026
• First Posted: May 14, 2026
• Study Start (Estimated): July 1, 2027
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

SA (3); JO (1); TU (2); QA (1); EG (4); MO (1); PA (1)