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NCT Number: NCT07562178

Pemafibrate for Symptomatic ICAS RCT

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

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Key information

Conditions

Intracranial Atherosclerotic Disease (ICAD) Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Dyslipidemias Hyperlipidemias Hypertriglyceridaemia Hypertriglyceridemia Lipid Metabolism Disorders Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Stroke Stroke (CVA) or TIA Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Iwate Medical University Hospital, Hizume, Iwate, Japan

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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. 7. Patients who have taken pemafibrate or any fibrate within 12 weeks prior to consent.

  • Patients with contraindications to iodinated contrast media. 9. Patients on dialysis. 10. Patients with a history of pancreatitis attributable to hypertriglyceridemia.
  • Patients with severe systemic comorbidities with an expected survival <12 months.
  • 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.

Treatment and study plan

Pemafibrate

Drug

Participants in this arm will receive pemafibrate in addition to standard medical therapy.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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

  3. Change in percent stenosis by the WASID method

    Time frame: Baseline and 12 months

  4. Proportion of intracranial arterial stenosis progression/improvement per the TOSS and TOSS-2 criteria

    Time frame: Baseline and 12 months

  5. Proportion of intracranial arterial stenosis progression/improvement per the Wong KS criteria

    Time frame: Baseline and 12 months

  6. 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

  7. All-cause mortality

    Time frame: From enrollment to the end of treatment at 12 months

  8. 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.

  9. Change in Fazekas scale on brain MRI

    Time frame: Baseline and 12 months

  10. Change in number of cerebral microbleeds on brain MRI

    Time frame: Baseline and 12 months

  11. Change in total cerebral small vessel disease score on brain MRI

    Time frame: Baseline and 12 months

  12. Changes in ankle-brachial index (ABI)

    Time frame: Baseline and 12 months

  13. Change in cardio-ankle vascular index (CAVI)

    Time frame: Baseline and 12 months

  14. Change in pulse wave velocity (PWV)

    Time frame: Baseline and 12 months

  15. 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

  16. Safety: occurrence of adverse events and illnesses

    Time frame: From enrollment to the end of treatment at 12 months

Study contacts

Contact information is provided by the study sponsor or research team.

Kenichi Todo, MD, PhD

CONTACT

[email protected]

+81-3-3353-8111

Takao Hoshino, MD, PhD

CONTACT

[email protected]

+81-3-3353-8111

Sponsors and collaborators

Lead sponsor

Tokyo Women's Medical University

Other

Collaborators

  • Kowa Company, Ltd.

Registry information

Official study 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)

Acronym: PPAR-ICAS

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
May 1, 2026
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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