Pemafibrate for Symptomatic ICAS RCT (PPAR-ICAS)

May 13, 2026 updated by: Kenichi Todo, Tokyo Women's Medical University

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Japan
    • Iwate
      • Hizume, Iwate, Japan, 028-3695
        • Not yet recruiting
        • Iwate Medical University Hospital
        • Contact:
    • Kagoshima-ken
      • Kagoshima, Kagoshima-ken, Japan, 892-0853
        • Not yet recruiting
        • Kagoshima Medical Center
        • Contact:
    • Kumamoto
      • Kumamoto, Kumamoto, Japan, 860-8556
    • Kyoto
      • Kyoto, Kyoto, Japan, 602-8566
        • Recruiting
        • University Hospital Kyoto Prefectural University of Medicine
        • Contact:
      • Kyoto, Kyoto, Japan, 602-8026
        • Not yet recruiting
        • Japanese Red Cross Kyoto Daini Hospital
        • Contact:
    • Nagasaki
      • Nagasaki, Nagasaki, Japan, 852-8501
        • Not yet recruiting
        • Nagasaki University Hospital
        • Contact:
    • Okayama-ken
      • Kurashiki, Okayama-ken, Japan, 701-0192
        • Not yet recruiting
        • Kawasaki Medical School Hospital
        • Contact:
    • Osaka
      • Hirakata, Osaka, Japan, 573-1191
        • Not yet recruiting
        • Kansai Medical University Hospital
        • Contact:
      • Osaka, Osaka, Japan, 540-0006
        • Not yet recruiting
        • Osaka National Hospital
        • Contact:
      • Osaka, Osaka, Japan, 558-8558
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Not yet recruiting
        • Saitama Medical University International Medical Center
        • Contact:
      • Saitama, Saitama, Japan, 330-8553
        • Not yet recruiting
        • Japanese Red Cross Saitama Hospital
        • Contact:
    • Tochigi
      • Mibu, Tochigi, Japan, 321-0293
        • Recruiting
        • Dokkyo Medical University Hospital
        • Contact:
      • Shimotsuke, Tochigi, Japan, 329-0498
        • Recruiting
        • Jichi Medical University Hospital
        • Contact:
    • Tokyo
      • Kodaira, Tokyo, Japan, 187-8510
      • Mitaka, Tokyo, Japan, 181-8611
        • Not yet recruiting
        • Kyorin University Hospital
        • Contact:
      • Shinjuku-Ku, Tokyo, Japan, 162-8666
        • Recruiting
        • Tokyo Women's Medical University Hospital
        • Contact:
      • Shinjuku-Ku, Tokyo, Japan, 160-0023
        • Not yet recruiting
        • Tokyo Medical University Hospital
        • Contact:
    • Yamanashi
      • Chūō, Yamanashi, Japan, 409-3898
        • Not yet recruiting
        • University of Yamanashi Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pemafibrate group
Participants in this arm will receive pemafibrate in addition to standard medical therapy.
Drug: Pemafibrate
Participants in this arm will receive pemafibrate in addition to standard medical therapy.
No Intervention: Non-pemafibrate group
Participants in this arm will receive standard medical therapy without pemafibrate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression in intracranial arterial stenosis on CTA at 12 months from enrollment (progression vs. no progression [no change or improvement])
Time Frame: 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.
Baseline and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Baseline and 12 months
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])
Time Frame: Baseline and 12 months
Baseline and 12 months
Change in percent stenosis by the WASID method
Time Frame: Baseline and 12 months
Baseline and 12 months
Proportion of intracranial arterial stenosis progression/improvement per the TOSS and TOSS-2 criteria
Time Frame: Baseline and 12 months
Baseline and 12 months
Proportion of intracranial arterial stenosis progression/improvement per the Wong KS criteria
Time Frame: Baseline and 12 months
Baseline and 12 months
Major cardiovascular events (MACE)
Time Frame: 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) 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
From enrollment to the end of treatment at 12 months
All-cause mortality
Time Frame: From enrollment to the end of treatment at 12 months
From enrollment to the end of treatment at 12 months
Change in Fazekas scale on brain MRI
Time Frame: Baseline and 12 months
Baseline and 12 months
Change in number of cerebral microbleeds on brain MRI
Time Frame: Baseline and 12 months
Baseline and 12 months
Change in total cerebral small vessel disease score on brain MRI
Time Frame: Baseline and 12 months
Baseline and 12 months
Changes in blood biomarkers
Time Frame: 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
Baseline, 3 months, 6 months, and 12 months
Safety: occurrence of adverse events and illnesses
Time Frame: From enrollment to the end of treatment at 12 months
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)
Time Frame: 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.
Baseline and 12 months
Changes in ankle-brachial index (ABI)
Time Frame: Baseline and 12 months
Baseline and 12 months
Change in cardio-ankle vascular index (CAVI)
Time Frame: Baseline and 12 months
Baseline and 12 months
Change in pulse wave velocity (PWV)
Time Frame: Baseline and 12 months
Baseline and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tokyo Women's Medical University

Collaborators

Kowa Company, Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

April 20, 2026

First Submitted That Met QC Criteria

April 25, 2026

First Posted (Actual)

May 1, 2026

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 13, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JIHS-C-005243-00

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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