Triglyceride-lowering Therapy With Pemafibrate for Prevention of Atherosclerotic Cardiovascular Disease in Patients With Symptomatic Intracranial Artery Stenosis: a Multi-center, Open-label, Randomized Controlled Trial (PPAR-ICAS)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 38
- 主要终点
- Progression in intracranial arterial stenosis on CTA at 12 months from enrollment (progression vs. no progression [no change or improvement])
研究概览
简要总结
The goal of this clinical trial is to learn whether pemafibrate can help prevent worsening of intracranial arterial stenosis (ICAS) in patients who have symptomatic ICAS and high triglycerides (TG) levels after ischemic stroke or transient ischemic attack (TIA).
The main questions this study aims to answer are:
- Does pemafibrate lower the chance that ICAS gets worse over 12 months?
- Does pemafibrate improve TG levels and other vascular risk markers?
- What are the effects of pemafibrate on vascular events, functional outcomes, and safety over 12 months?
Researchers will compare a pemafibrate group with a non-pemafibrate group to see whether pemafibrate helps prevent progression of ICAS. This is an open-label, randomized, parallel-group trial. That means participants are assigned by chance to 1 of 2 groups, and both the researchers and participants know which group was assigned. Participants in both groups will continue to receive standard stroke care, including antithrombotic therapy and management of vascular risk factors such as blood pressure, low-density lipoprotein cholesterol, diabetes, and smoking.
Participants may be eligible if they are 18 years or older, have clinically stable ischemic stroke or TIA, have 50% to 99% stenosis in a symptomatic intracranial artery on contrast-enhanced CT angiography (CTA), and have elevated fasting (>=150 mg/dL) or non-fasting (>=175 mg/dL) TG levels. Some people will not be eligible, such as those with ICAS due to non-atherosclerotic arterial disease, severe extracranial carotid stenosis, recent intravenous thrombolysis or mechanical thrombectomy, planned revascularization, contraindications to pemafibrate or iodinated contrast media, dialysis, or pregnancy.
Participants will:
- Be randomly assigned to a pemafibrate group or a non-pemafibrate group
- Take pemafibrate for 12 months if assigned to the pemafibrate group, with possible dose adjustment based on TG levels and kidney function
- Have blood tests and clinical assessments at baseline and during follow-up
- Undergo brain CTA at study entry and again at 12 months
- Undergo brain MRI/MRA and vascular tests such as ankle brachial index, cardio ankle vascular index, and pulse wave velocity according to the study schedule
- Be followed for vascular events, functional outcome, and adverse events for 1 year
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically stable ischemic stroke or high-risk TIA (ABCD2 score >=4) between 24 hours and 3 years from onset at enrollment.
- •Contrast-enhanced CT angiography (CTA) within 3 months prior to consent demonstrating 50-99% stenosis (WASID criteria) in a symptomatic intracranial artery: intracranial internal carotid artery, middle cerebral artery (M1/M2), anterior cerebral artery (A1), vertebral artery (V4), basilar artery, or posterior cerebral artery (P1).
- •Fasting triglycerides (TG) 150-499 mg/dL, or non-fasting TG 175-499 mg/dL, measured within 4 weeks prior to consent.
- •Men or women aged >=18 years at the time of consent.
- •Ability to obtain written informed consent from the patient or a legally authorized representative.
排除标准
- •Patients with intracranial arterial stenosis due to non-atherosclerotic disorders (e.g., vasculitis, moyamoya disease, intracranial arterial dissection).
- •Patients with >=70% stenosis of the extracranial carotid artery (NASCET criteria).
- •Patients with neurological deterioration within 24 hours prior to enrollment.
- •Patients who received intravenous thrombolysis or mechanical thrombectomy within 24 hours prior to enrollment.
- •Patients scheduled to undergo revascularization procedures (percutaneous transluminal angioplasty, stent placement, carotid endarterectomy, or cerebral bypass surgery).
- •Patients who meet any contraindication to pemafibrate, including:
- •(1) History of hypersensitivity to pemafibrate; (2) Severe hepatic impairment or liver cirrhosis classified as Child-Pugh B or C; (3) Cholelithiasis; (4) Pregnancy or suspected pregnancy; (5) Concomitant use of cyclosporine or rifampin.
- •Patients who have taken pemafibrate or any fibrate within 12 weeks prior to consent.
- •8. Patients with contraindications to iodinated contrast media.
- •Patients on dialysis.
- •Patients with a history of pancreatitis attributable to hypertriglyceridemia.
- •11. Patients with severe systemic comorbidities with an expected survival <12 months.
- •12. Patients who may be pregnant, are pregnant, or are breastfeeding.
- •Any other condition for which the principal or sub-investigator judges participation to be inappropriate.
研究组 & 干预措施
Pemafibrate group
Participants in this arm will receive pemafibrate in addition to standard medical therapy.
干预措施: Pemafibrate (Drug)
Non-pemafibrate group
Participants in this arm will receive standard medical therapy without pemafibrate.
结局指标
主要结局
Progression in intracranial arterial stenosis on CTA at 12 months from enrollment (progression vs. no progression [no change or improvement])
时间窗: Baseline and 12 months
Stenosis is assessed by the WASID method; progression is defined as an absolute increase of \>=10 percentage points in percent stenosis or the development of occlusion, stability as a change of \<10 percentage points in either direction, and improvement as an absolute decrease of \>=10 percentage points. If, during follow-up, emergency or unplanned revascularization (mechanical thrombectomy, percutaneous transluminal angioplasty, stent placement, or bypass surgery) is performed for the target culprit vessel lesion evaluated at registration in relation to progression or occlusion of that lesion, the case will be classified as "progression" regardless of the availability of CTA findings at 12 months.
次要结局
- Major cardiovascular events (MACE)(From enrollment to the end of treatment at 12 months)
研究者
Kenichi Todo
Professor
Tokyo Women's Medical University