Trial of PCSK9 Inhibition in Patients with Acute Stroke and Symptomatic Intracranial Atherosclerosis

NCT ID: NCT05001984

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-01
• Study Completion Date: 2025-04-15

Brief Summary

This study will evaluate whether low-density lipoprotein (LDL-C) lowering with alirocumab results in greater change from baseline in intracranial atherosclerotic plaque at week 26 than control in adults with acute ischemic stroke from intracranial atherosclerosis taking lipid lowering therapy.

Detailed Description

In this trial, we will conduct a prospective, randomized, open-label, blinded end-point study using high-resolution MRI in patients with acute ischemic stroke from intracranial atherosclerosis to evaluate the efficacy and safety of alirocumab. We hypothesis that additional alirocumab treatment on a background of statin therapy could result in greater stabilization of intracranial plaque and regression of arterial stenosis.

Conditions

Intracranial Atherosclerosis; Acute Ischemic Stroke; ICAS - Intracranial Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intervention group

In addition to high-intensity statin and antiplatelet treatment, patients will receive treatment of alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks

Group Type: ACTIVE_COMPARATOR

Alirocumab

Intervention Type: DRUG

Alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks.

Control group

Patient will have high-intensity statin and antiplatelet treatment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Alirocumab

Alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks.

Intervention Type: DRUG

Other Intervention Names

Praluent

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score of 1-15
• Ischemic lesions on diffuse-weighted imaging located in the territory of symptomatic intracranial atherosclerosis (ICAS).
• Symptomatic ICAS (above 30%) at the M1 or M2 of the middle cerebral artery, basilar artery or at the intracranial portion of the internal carotid artery or vertebral artery.
• Serum LDL-C ≥70 mg/dL for subjects on lipid-lowering therapies (such as a statin and/or ezetimibe) or LDL-C ≥100 mg/dL for subjects without lipid-lowering therapies.
• Ability to randomize within 7 days of time last known free of new ischemic symptoms.
• Ability to receive alirocumab or statin treatment within 7 days of stroke onset.
• Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
• Pre-stroke modified Rankin Scale (mRS)≦2

Exclusion Criteria

• Age <20 years.
• Judged by clinical physician.
• After endovascular intervention or endarterectomy for the symptomatic ICAS.
• Patients with more than 50% stenosis of extra-cranial arteries the relevant arteries on magnetic resonance angiography (MRA), including extra-cranial carotid artery or vertebral arteries.
• Patients with high risk of cardioembolic source, such as atrial fibrillation, acute myocardial infarction, severe heart failure or valvular heart disease.
• Other determined stroke etiology, such as vasculitis, shock, antiphospholipid antibody syndrome, arterial dissection, CADASIL and etc.
• Qualifying ischemic event induced by angiography or surgery.
• Severe non-cardiovascular comorbidity with life expectancy <6 months.
• Contraindication or allergy to alirocumab or Gadolinium
• Severe renal (serum creatinine >2 mg/dL) or calculated glomerular filtration rate <30 mL/min/ 1.73 m2 by estimated glomerular filtration rate (eGFR) using Cockcroft Gault methodology.
• Hepatic insufficiency (INR>1.2; ALT>40 U/L or any resultant complication, such as variceal bleeding, encephalopathy, or jaundice)
• Hemostatic disorder or systemic bleeding in the past 3 months
• Current thrombocytopenia (platelet count <100 x109/L) or leukopenia (<2 x109/L)
• Anemia（<10 mg/dL）
• History of drug-induced hematologic or hepatic abnormalities
• History of malignancy that required surgery, radiation therapy or systemic therapy.
• Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use effective contraception.
• Other neurological conditions that would complicate assessment of outcomes during follow-up.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung University

OTHER

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yenchu Huang, MD

Role: STUDY_DIRECTOR

Chang Gung Memorial Hospital, Chiayi

Locations

Yenchu Huang

Chiayi City, Taiwan, Taiwan

Countries

Taiwan

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Other Identifiers

MOST 110-2314-B-182A-072

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TOPICAL-MRI

Identifier Type: -

Identifier Source: org_study_id