Clinical trial NCT05001984: Trial of PCSK9 Inhibition in Patients with Acute Stroke and Symptomatic Intracranial Atherosclerosis
Official title: Trial of PCSK9 Inhibition in Patients with Acute Stroke and Symptomatic Intracranial Atherosclerosis - a Prospective, Randomized, Open-label, Blinded End-point Study with High-resolution MR Vessel Wall Imaging
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Intracranial Atherosclerosis
Acute Ischemic Stroke
ICAS - Intracranial Atherosclerosis
Keywords: Intracranial Atherosclerosis
Acute Ischemic Stroke
PCSK9 inhibitor
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
Collaborators: name: Chang Gung University
First posted: 2021-08-12
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, open-label, blinded end-point study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The changes of intracranial atherosclerotic plaque: stenosis degree
timeFrame: 26 weeks
measure: The changes of intracranial atherosclerotic plaque: percent atheroma volume
timeFrame: 26 weeks
measure: The changes of intracranial atherosclerotic plaque: enhancement volume
timeFrame: 26 weeks
Secondary outcomes:
measure: Percentage of patients with major cardiovascular events
timeFrame: 26 weeks
measure: Percentage of patients with myocardial infarction
timeFrame: 26 weeks
measure: Percentage of patients with cardiovascular death
timeFrame: 26 weeks
measure: Percentage of patients with stroke
timeFrame: 26 weeks
measure: Percentage of patients with ischemic stroke or transient ischemic attack.
timeFrame: 26 weeks
measure: Percentage of patients with new ischemic lesions
timeFrame: 26 weeks
measure: Percentage of patients with favorable functional recovery
timeFrame: 3 months
measure: Changes in serum biomarkers
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Chiayi City
country: Taiwan
facility: Yenchu Huang
Study officials:
affiliation: Chang Gung Memorial Hospital, Chiayi
name: Yenchu Huang, MD
role: STUDY_DIRECTOR
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