Evolocumab Added to Statin Therapy in Patients With Symptomatic Intracranial Atherosclerotic Stenosis (EAST-ICAS)---a Pilot Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Remodeling index (RI) of the plaque
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
investigator-initiated, open-label, blinded endpoint assessment, controlled, randomized pilot trial
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Evolocumab added to statin therapy
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.
干预措施: Evolocumab (Drug)
Evolocumab added to statin therapy
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.
干预措施: Atorvastatin (Drug)
Statin therapy
Atorvastatin 20-40mg. Anti-platelet aggregation and risk factor management in both arms.
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Remodeling index (RI) of the plaque
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- 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.)
研究者
Lu Hua
Professor
The First Affiliated Hospital with Nanjing Medical University