Carotid StenosisPhase 3CAROTID-STABILNCT07586540
Alirocumab for Stabilisation of Symptomatic Vulnerable Carotid Plaque
A Phase 3 study testing Alirocumab and Atorvastatin in people with Carotid Stenosis, run by Middle East North Africa Stroke and Interventional Neurotherapies Organization at 14 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Carotid Stenosis
- What is being tested?
- Alirocumab and Atorvastatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 14 sitesin 8 countries
- Study dates
- Jul 2027to Sep 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
14 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
14 sites in 8 countries
Egypt4 sites
Alexandria University, Smouha University Comprehensive Stroke Center
Alexandria
Ain Shams University
Cairo
Cairo University
Cairo
Neurology Department, Al-Azhar University
Cairo
Saudi Arabia3 sites
King Khalid University
Abhā
King Abdulaziz Medical City
Jeddah
King Abdullah Medical City
Mecca
Turkey (Türkiye)2 sites
Department of Neurology, Eskisehir Osmangazi University
Eskişehir
Neurology Department, Dr. Lutfi Kirdar City Hospital
Istanbul
About this study
Official title: 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.
Read the 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.
- Conditions
- Carotid Stenosis
- Being tested
- Alirocumab, Placebo, Atorvastatin
- Keywords
- vulnerable plaque, alirocumab, PCSK9 inhibitor
- Medical subject headings
- Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
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.
PlaceboDrug
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.
AtorvastatinDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Alirocumab; Drug: Placebo; Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 26 weeks
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Randomisation to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2026
- Study startJul 2027 (estimated)
- Primary completionMar 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid StenosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Middle East North Africa Stroke and Interventional Neurotherapies Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ossama Mansour, Alexandria University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07586540
- Sponsor's protocol ID
- MENASINO-CAROTID-2026-01
- Acronym
- CAROTID-STABIL
- Status last verified
- May 2026
- First submitted
- 8 May 2026
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided