Recruiting
Phase 4
PCSK9 Inhibitor With Statin Therapy for Asymptomatic Intracranial Atherosclerosis
Condition(s) studied
Intracranial AtherosclerosisIntracranial Artery StenosisAtherosclerotic Plaque
Investigational drug(s) / intervention(s)
Recaticimab and StatinStatin
Recaticimab and Statin: Recaticimab (450mg every 12 weeks subcutaneously) combined with rosuvastatin 10mg qn or atorvastatin 20mg qn
Statin: Rosuvastatin 10mg qn or atorvastatin 20mg qn
Study summary
This is a prospective, multicenter, open-label, blinded-endpoint, randomized controlled trial designed to evaluate the efficacy and safety of PCSK9 inhibitor combined with statin therapy compared to statin monotherapy in reversing asymptomatic intracranial atherosclerosis, assessed using high-resolution magnetic resonance imaging of the intracranial vessel walls.
Eligibility
Inclusion Criteria:
1. Age ≥18 and ≤80, male or female;
2. Asymptomatic intracranial artery stenosis (50%-99%) in the internal carotid artery (C6-7 segments), middle cerebral artery (M1 segment), vertebral artery (V4 segment), or basilar artery, confirmed by angiography (MRA, CTA, or DSA);
3. Atherosclerosis identified as the cause of intracranial artery stenosis by high-resolution magnetic resonance imaging;
4. No previous ischemic cerebrovascular events (including ischemic stroke or transient ischemic attack).
5. Baseline low-density lipoprotein cholesterol ≥ 1.8 mmol/L;
6. Informed consent signed.
Exclusion Criteria:
1. Non-atherosclerotic intracranial artery stenosis, including arterial dissection; moya moya disease; systemic vasculitis and primary central nervous system vasculitis; varicella-zoster vasculopathy or other viral vasculopathy; neurosyphilis and other intracranial infections, radiation vasculopathy; fibromuscular dysplasia, sickle cell disease, neurofibromatosis; reversible cerebral vasoconstriction syndrome; postpartum vasculopathy; suspected vasospasm, suspected reperfusion after vessel occlusion.
2. Upstream tandem extracranial vessel stenosis (≥50%) adjacent to the target intracranial stenotic vessel.
3. Previous treatment of target intracranial lesion with endovascular intervention or plan to perform endovascular intervention within 6 months, including intracranial stenting, endovascular angioplasty, and thrombectomy.
4. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, extradural, intraventricular) within 90 days prior to enrollment.
5. Presence of intracranial tumors.
6. Presence of cerebral aneurysms or arteriovenous malformations with indications for interventional therapy.
7. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 6 months after enrollment.
8. Presence of any of the following unequivocal cardiac sources of embolism: mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, chronic or paroxysmal atrial fibrillation.
9. New York Heart Association (NYHA) class III or IV, or known left ventricular ejection fraction \< 30%.
10. Severe liver dysfunction or severe kidney dysfunction: AST and/or ALT \> 3 times the ULN; creatinine clearance \< 0.6 mL/s and/or serum creatinine \> 265 μmol/L (\>3.0 mg/dL); CK \>5 times the ULN at screening.
11. Active bleeding diathesis or coagulopathy (e.g., active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count \< 125,000 / uL, hematocrit \< 30%, Hgb \< 10 g/dl, international normalized ratio \>1.5, bleeding time \> 1 minute beyond normal value upper limit).
12. Presence of systemic autoimmune diseases: systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, Behçet's disease, mixed connective tissue disease, IgG4-related disease.
13. Dementia or psychiatric problem that hinder their ability to consistently adhere to an outpatient program. Co-morbid conditions that may limit the life expectancy to less than 3 years.
14. Relative/absolute contraindications to magnetic resonance imaging (MRI) (such as presence of internal metallic objects, claustrophobia, contrast agent allergy, severe renal impairment, epilepsy, hypotension, asthma, and other hypersensitivity respiratory diseases).
15. Uncontrolled hypertension during the screening period, defined as seated systolic blood pressure (SBP) \> 180 mmHg or diastolic blood pressure (DBP) \> 110 mmHg.
16. Prior use of PCSK9 inhibitor before this recruitment.
17. Known intolerance or allergy to statin.
18. Pregnancy, lactation, or planning pregnancy.
19. Currently participating in another study.
Primary outcome measure(s)
- Change in plaque burden from baseline to week 24 — From baselie to the end of treatment at 24 weeks
Intracranial plaque burden was assessed at maximum stenosis site by high-resolution magnetic resonance imaging, performed at baseline and the end of the treatment period (24 \[±1\] week) on the same machine. The plaque burden is calculated according to the following formula: plaque burden = \[(vessel wall cross-sectional area - lumen cross-sectional area ) / vessel wall cross-sectional area\] ×100%. The outcome will be centrally assessed by an independent core imaging laboratory blinded to treatment allocation according to a predefined imaging analysis protocol.
Trial sites (19)
| Facility | City | Region | Status |
| Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College |
Beijing |
Beijing Municipality |
Recruiting |
| Chinese PLA General Hospital |
Beijing |
Beijing Municipality |
Not Yet Recruiting |
| The Third Affiliated Hospital of Sun Yat-sen University, Yuedong Hospital |
Meizhou |
Guangdong |
Not Yet Recruiting |
| Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine |
Cangzhou |
Hebei |
Not Yet Recruiting |
| Peking University Third Hospital Qinhuangdao Hospital |
Qinhuangdao |
Hebei |
Not Yet Recruiting |
| Hebei Provincial People's Hospital |
Shijiazhuang |
Hebei |
Recruiting |
| Tangshan Worker's Hospital |
Tangshan |
Hebei |
Not Yet Recruiting |
| First Affiliated Hospital of Harbin Medical University |
Harbin |
Heilongjiang |
Not Yet Recruiting |
| The first affiliated hospital of zhengzhou university |
Zhengzhou |
Henan |
Not Yet Recruiting |
| Taihe Hospital |
Shiyan |
Hubei |
Not Yet Recruiting |
| Zhongnan Hospital of Wuhan University |
Wuhan |
Hubei |
Not Yet Recruiting |
| Baotou Central Hospital |
Baotou |
Inner Mongolia |
Not Yet Recruiting |
| Nanjing First Hospital |
Nanjing |
Jiangsu |
Not Yet Recruiting |
| Jining First People's Hospital |
Jining |
Shandong |
Not Yet Recruiting |
| Liaocheng People's Hospital |
Liaocheng |
Shandong |
Not Yet Recruiting |
| The Affiliated Hospital of Qingdao University |
Qingdao |
Shandong |
Not Yet Recruiting |
| Weifang People's Hospital |
Weifang |
Shandong |
Not Yet Recruiting |
| Chongqing General Hospital |
Chongqing |
China |
Not Yet Recruiting |
| Huashan Hospital, Fudan University |
Shanghai |
China |
Not Yet Recruiting |
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