PCSK9 Inhibitor With Statin Therapy for Asymptomatic Intracranial Atherosclerosis
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-80
SponsorPeking Union Medical College Hospital
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 and ≤80, male or female;
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);
Atherosclerosis identified as the cause of intracranial artery stenosis by high-resolution magnetic resonance imaging;
No previous ischemic cerebrovascular events (including ischemic stroke or transient ischemic attack).
Disqualifiers
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.
Upstream tandem extracranial vessel stenosis (≥50%) adjacent to the target intracranial stenotic vessel.
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.
Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, extradural, intraventricular) within 90 days prior to enrollment.
Trial design
Design model
Parallel
Treatments tested in this trial
Recaticimab and Statin
DrugRecaticimab (450mg every 12 weeks subcutaneously) combined with rosuvastatin 10mg qn or atorvastatin 20mg qn
Statin
DrugRosuvastatin 10mg qn or atorvastatin 20mg qn
Treatment groups
300 Participants
are divided into 2 treatment groupsGroup A: Recaticimab plus Statin GroupExperimental treatment 1 intervention
Group B: Statin GroupActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in plaque burden from baseline to week 24
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.
Time frame
From baselie to the end of treatment at 24 weeksSecondary outcomes
1
Change in stenosis degree from baseline to week 24
The degree of stenosis is calculated according to the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criteria using the formula: \[1-(Dstenosis/Dnormal)\]×100%. Dstenosis represents the vessel diameter at the most stenotic site of the intracranial artery, and Dnormal represents the normal vessel diameter at a reference site.
Time frame
From baseline to the end of treatment at 24 weeks2
Time from randomization to the first-ever ischemic stroke or transient ischemic attack
Ischemic Stroke: Defined as an acute cerebral infarction with clinical signs or imaging evidence of a new acute focal neurological injury persisting for more than 24 hours, excluding other non-ischemic causes. Transient Ischemic Attack (TIA): Defined as a sudden onset of focal neurological deficit due to cerebral or retinal ischemia, which completely resolves within 24 hours. Imaging (CT or MRI) must show no evidence of a new cerebral infarction. Other non-ischemic causes, such as brain infection, trauma, tumor, epilepsy, severe metabolic disorders, or progressive neurological diseases, must be excluded.
Time frame
From baseline to the end of treatment at 24 weeks3
Change in plasma marker glial fibrillary acidic protein(GFAP)
Change in plasma marker glial fibrillary acidic protein(GFAP) quantified using the Single Molecule Array platform from baseline to the end of treatment at 24 weeks
Time frame
From baseline to the end of treatment at 24 weeks4
Change in plasma marker neurofilament light(NfL)
Change in plasma marker Neurofilament light(NfL) quantified using the Single Molecule Array platform from baseline to the end of treatment at 24 weeks
Time frame
From baseline to the end of treatment at 24 weeksOther outcomes
1
Time from randomization to the time of the first occurrence of transient ischemic attack
Transient Ischemic Attack (TIA): Defined as a sudden onset of focal neurological deficit due to cerebral or retinal ischemia, which completely resolves within 24 hours. Imaging (CT or MRI) must show no evidence of a new cerebral infarction. Other non-ischemic causes, such as brain infection, trauma, tumor, epilepsy, severe metabolic disorders, or progressive neurological diseases, must be excluded.
Time frame
From baseline to the end of treatment at 24 weeks2
Time from randomization to the time of the first occurrence of ischemic stroke
Ischemic Stroke: Defined as an acute cerebral infarction with clinical signs or imaging evidence of a new acute focal neurological injury persisting for more than 24 hours, excluding other non-ischemic causes.
Time frame
From baseline to the end of treatment at 24 weeks3
Time from randomization to the time of the occurrence of any stroke
Any stroke includes ischemic and hemorrhagic stroke
Time frame
From baseline to the end of treatment at 24 weeks4
Time from randomization to the time of the occurrence of myocardial infarction
Time from randomization to the time of the occurrence of myocardial infarction
Time frame
From baseline to the end of treatment at 24 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Peking Union Medical College Hospital
Lead sponsor
Chinese PLA General Hospital
Collaborator
Hebei General Hospital
Collaborator
Taihe Hospital
Collaborator
Weifang People's Hospital
Collaborator
Nanjing First Hospital, Nanjing Medical University
Collaborator
Baotou Central Hospital
Collaborator
Jining First People's Hospital
Collaborator
Liaocheng People's Hospital
Collaborator
Tangshan Worker's Hospital
Collaborator
Chongqing General Hospital
Collaborator
First Affiliated Hospital of Harbin Medical University
Collaborator
Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine
Collaborator
The First Affiliated Hospital of Zhengzhou University
Collaborator
The Affiliated Hospital of Qingdao University
Collaborator
Zhongnan Hospital
Collaborator
Huashan Hospital
Collaborator
Source ClinicalTrials.gov