Hypertriglyceridaemia, Intracranial Atherosclerotic Disease (ICAD), Stroke (CVA) or TIA
Conditions
Brief summary
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: 1. Does pemafibrate lower the chance that ICAS gets worse over 12 months? 2. Does pemafibrate improve TG levels and other vascular risk markers? 3. 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
Interventions
DRUGPemafibrate
Participants in this arm will receive pemafibrate in addition to standard medical therapy.
Sponsors
Tokyo Women's Medical University
Kowa Company, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Clinically stable ischemic stroke or high-risk TIA (ABCD2 score \>=4) between 24 hours and 3 years from onset at enrollment. 2. 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). 3. Fasting triglycerides (TG) 150-499 mg/dL, or non-fasting TG 175-499 mg/dL, measured within 4 weeks prior to consent. 4. Men or women aged \>=18 years at the time of consent. 5. Ability to obtain written informed consent from the patient or a legally authorized representative.
Exclusion criteria
1. Patients with intracranial arterial stenosis due to non-atherosclerotic disorders (e.g., vasculitis, moyamoya disease, intracranial arterial dissection). 2. Patients with \>=70% stenosis of the extracranial carotid artery (NASCET criteria). 3. Patients with neurological deterioration within 24 hours prior to enrollment. 4. Patients who received intravenous thrombolysis or mechanical thrombectomy within 24 hours prior to enrollment. 5. Patients scheduled to undergo revascularization procedures (percutaneous transluminal angioplasty, stent placement, carotid endarterectomy, or cerebral bypass surgery). 6. 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. 7. Patients who have taken pemafibrate or any fibrate within 12 weeks prior to consent. 8\. Patients with contraindications to iodinated contrast media. 9. Patients on dialysis. 10. 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. 13. Any other condition for which the principal or sub-investigator judges participation to be inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression in intracranial arterial stenosis on CTA at 12 months from enrollment (progression vs. no progression [no change or improvement]) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key secondary endpoint (supplementary analyses of the primary endpoint): Change in intracranial arterial stenosis on CTA at 12 months from enrollment (three categories: progression, no change, improvement) | Baseline and 12 months | — |
| Key secondary endpoint (supplementary analyses of the primary endpoint): Improvement in intracranial arterial stenosis on CTA at 12 months from enrollment (improvement vs. no improvement [progression or no change]) | Baseline and 12 months | — |
| Change in percent stenosis by the WASID method | Baseline and 12 months | — |
| Proportion of intracranial arterial stenosis progression/improvement per the TOSS and TOSS-2 criteria | Baseline and 12 months | — |
| Proportion of intracranial arterial stenosis progression/improvement per the Wong KS criteria | Baseline and 12 months | — |
| Major cardiovascular events (MACE) | From enrollment to the end of treatment at 12 months | The following individual events and their composite: Ischemic stroke (fatal, nonfatal), TIA, intracranial hemorrhage (fatal, nonfatal), any stroke (ischemic stroke, TIA, intracranial hemorrhage), emergency or unplanned revascularization procedures, including mechanical thrombectomy, percutaneous transluminal angioplasty, stent placement, or bypass surgery Myocardial infarction (fatal, nonfatal), any coronary artery disease event (myocardial infarction, or angina treated with PCI or CABG) Symptomatic peripheral artery disease (with intermittent claudication, ulceration, or gangrene; or requiring revascularization) Vascular death |
| All-cause mortality | From enrollment to the end of treatment at 12 months | — |
| Activities of daily living by mRS score (mRS 0-1, 0-2, and 0-3 proportions, and the overall mRS score distribution) | Baseline and 12 months | The modified Rankin Scale (mRS) ranges from 0 to 6, with higher scores indicating greater disability or death; therefore, higher scores indicate a worse outcome. |
| Change in Fazekas scale on brain MRI | Baseline and 12 months | — |
| Change in number of cerebral microbleeds on brain MRI | Baseline and 12 months | — |
| Change in total cerebral small vessel disease score on brain MRI | Baseline and 12 months | — |
| Changes in ankle-brachial index (ABI) | Baseline and 12 months | — |
| Change in cardio-ankle vascular index (CAVI) | Baseline and 12 months | — |
| Change in pulse wave velocity (PWV) | Baseline and 12 months | — |
| Changes in blood biomarkers | Baseline, 3 months, 6 months, and 12 months | Complete blood count; fasting TG, HDL-C, LDL-C, RLP-C; apolipoprotein C-III; lipoprotein(a); fasting plasma glucose; HbA1c; AST, ALT, gamma-GTP; creatinine, eGFR; CK; CRP, high-sensitivity CRP; IL-6; total homocysteine; PT-INR; APTT; fibrinogen; D-dimer |
| Safety: occurrence of adverse events and illnesses | From enrollment to the end of treatment at 12 months | — |
Countries
Japan
Contacts
CONTACTKenichi Todo, MD, PhD
CONTACTTakao Hoshino, MD, PhD
Outcome results
None listed