Pemafibrate for Symptomatic ICAS RCT

ClinicalTrials.gov ID

NCT07562178

Lead Sponsor

Tokyo Women's Medical UniversityOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Not Applicable

Enrollment

270Estimated

Last Update Posted

Aug 3, 2026Actual

Start Date

May 26, 2026Actual

Primary Completion Date

Mar 31, 2028Estimated

Completion Date

Dec 31, 2028Estimated

Official Title

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)

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

• Intracranial Atherosclerotic Disease (ICAD)
• Hypertriglyceridaemia
• Stroke (CVA) or TIA

• Pemafibrate

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Single

Lead Sponsor

Tokyo Women's Medical UniversityOTHER

Collaborators

Kowa Company, Ltd.INDUSTRY

ritabash@iwate-med.ac.jp+81-19-613-7111

hmatsuok0124@yahoo.co.jp+81-99-223-1151

ytate@nagasaki-u.ac.jp+81-95-819-7200

s-okazaki@osaka-njm.net+81-6-6942-1331

y.m.since20150916@gmail.com+81-6-6771-6051

sakaguti@neurol.med.osaka-u.ac.jp+81-6-6692-1201

tanaka19830311kanta@gmail.com+81-72-288-7222

take@dokkyomed.ac.jp+81-282-86-1111

honma.yutaka@showa-hp.jp+81-42-461-0052

terry@ks.kyorin-u.ac.jp+81-422-47-5511

• PCSK9 Inhibitor With Statin Therapy for Asymptomatic Intracranial Atherosclerosis

  NCT06902740

  RecruitingInterventionalPhase 4Updated Jun 12, 2026
• PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke

  NCT07466251

  Not yet recruitingInterventionalPhase 4Updated Jul 15, 2026
• Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2×2 Randomized Controlled Trial

  NCT07605130

  Not yet recruitingInterventionalPhase 4Updated May 22, 2026
• IntraCranial Angiography-derived Fraction Flow-guided Percutaneous Transluminal Angioplasty and Stenting Versus Medical Therapy (ICAS-MT)

  NCT05974033

  Not yet recruitingInterventionalNot ApplicableUpdated Aug 3, 2023
• Angioplasty and Stenting for Patients With Symptomatic Intracranial Atherosclerosis

  NCT02689037

  Unknown statusInterventionalPhase 3Updated Apr 5, 2016
• Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

  NCT00130039

  CompletedInterventionalPhase 4Updated Jan 12, 2010