Evolocumab Added to Statin Therapy in Symptomatic Intracranial Atherosclerotic Stenosis (EAST-ICAS)
- Conditions
- Stroke Patients With Symptomatic Intracranial Atherosclerotic Stenosis
- Interventions
- Registration Number
- NCT05741086
- Brief Summary
The primary goal of the trial is to investigate whether the experimental arms (receiving the Proprotein Convertase Subtilisin-Kexin Type 9 \[PCSK9\] inhibitor Evolocumab plus statin) could cause more changes from baseline in intracranial atherosclerotic plaque and hemodynamic features during 1 year of follow-up, compared with the control arm (taking statin) in patients with recent stroke/transient ischemic attack (TIA) caused by intracranial artery stenosis.
- Detailed Description
Intracranial atherosclerosis stenosis (ICAS) is one of the most common causes of stroke worldwide and is particularly prevalent in Asian. It accounts for up to 30-50% of strokes amongst Asian patient cohorts, in contrast to 5-10% of strokes amongst western patient cohorts. The SAMMPRIS established aggressive medical management (Intensive lipid lowering with statin to reach a low-density lipoprotein (LDL)-cholesterol lower than 1.8mmol/L, et al) as a superior choice for symptomatic ICAS compared to the percutaneous transluminal angioplasty and stenting. However, around 15% still had recurrent stroke or death during a median follow-up of 32.4 months in SAMMPRIS study in the aggressive medical management group.
Evolocumab, a member of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%. The FOURIER study showed that Evolocumab reduced the risk of cardiovascular events (e.g. cardiovascular death, myocardial infarction and stroke), in patients with atherosclerotic cardiovascular disease.
The proposed pilot study will recruit 80 patients with recent stroke/transient ischemic attack (TIA) caused by intracranial artery stenosis, and directly compare Evolocumab on top of statin with statin therapy in changes of intracranial atherosclerotic plaque and hemodynamic features during 1 year of follow-up.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Evolocumab added to statin therapy Evolocumab Evolocumab (140 mg every 2 weeks for 1 year) added to statin (Atorvastatin 20-40mg). Anti-platelet aggregation and risk factor management in both arms. Evolocumab added to statin therapy Atorvastatin Evolocumab (140 mg every 2 weeks for 1 year) added to statin (Atorvastatin 20-40mg). Anti-platelet aggregation and risk factor management in both arms. Statin therapy Atorvastatin Atorvastatin 20-40mg. Anti-platelet aggregation and risk factor management in both arms.
- Primary Outcome Measures
Name Time Method Remodeling index (RI) of the plaque This will be assessed at 1 year after recruitment. the outer wall area (OWA) is manually contoured on T1-weighted SPACE at the most stenotic site (OWAplaque) and the reference site (OWAreference). RI is calculated as OWAplaque/OWAreference × 100%. Arterial remodeling is categorized as positive if RI \> 1.05, intermediate if 0.95 ≤ RI ≤ 1.05, and negative if RI \< 0.95;
Plaque burden (PB) This will be assessed at 1 year after recruitment. lumen area (LA) is manually contoured on T1-weighted SPACE at the most stenotic site (LAplaque). PB is calculated as (1 - LAplaque/OWAplauqe) × 100%
Plaque enhancement This will be assessed at 1 year after recruitment. grading of plaque enhancement: grade 0 indicated enhancement is similar to or less than that of normal-appearing intracranial arterial walls in the same individual; grade 1, enhancement is greater than that of grade 0 but less than that of the pituitary infundibulum; and grade 2, enhancement is similar to or greater than that of the infundibulum. plaque enhancement ratio (ER): circular region of interest (ROI) was drawn within the plaque on pre-contrast and post-contrast T1-weighted SPACE images, respectively. The mean signal intensity (SI) of plaques were obtained. ER = (SIpost - SIpre)/SIpre ×100%
Presence of T1 hyperintensity in the plaque This will be assessed at 1 year after recruitment. the brightest spot of the plaque with SI \>150% of that of the reference vessel wall on pre-contrast T1 image
Hemodynamic characteristics: Hypoperfusion volume This will be assessed at 1 year after recruitment. dynamic susceptibility contrast-perfusion weighted imaging (DSC-PWI) performed and computed using the singular value decomposition deconvolution method using a commercial software NeuBrainCARE (v1.1.10). Hypoperfusion volume on the ipsilateral side of stroke were automatically calculated by use of time to maximum (Tmax) with time thresholds of \> 4 seconds and \> 6 seconds, respectively.
Plaque distribution: whether it is a concentric plaque or not This will be assessed at 1 year after recruitment. a concentric plaque is defined if the wall involvement was more than 75%, and the minimum wall thickness is higher than 50% of the maximum wall thickness.
Degree of stenosis caused by the plaque This will be assessed at 1 year after recruitment. degree of stenosis = (1 - Dplaque/Dreference) × 100%, where Dplaque indicated the diameter of the culprit artery at the most stenotic site, and Dreference was the diameter of the normal artery proximal to the plaque
- Secondary Outcome Measures
Name Time Method Changes in LDL-cholesterol levels This will be assessed during the first year of follow-up. any stroke (ischemic or hemorrhagic) or death during 1 year of follow-up in an intention-to treat analysis. This will be assessed during the first year of follow-up.
Trial Locations
- Locations (1)
the First affiliated hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China