Effect of Pemafibrate and Rosuvastatin or Rosuvastatin Alone on Lipid Core Plaques in Coronary Artery Disease Evaluated by Near-infrared Spectroscopy Intravascular Ultrasound

JRCT ID: jRCT1051190122

Registered date:19/03/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: coronary artery disease
• Date of first enrollment: 19/03/2020
• Target sample size: 46
• Study type: Interventional

Intervention(s)

Patients in the pemafibrate arm will receive pemafibrate 0.4 mg/day in addition to statin therapy (rosuvastatin 10 mg/day).
Patients in the standard-of-care arm will receive rosuvastatin 10 mg/day.

Outcome(s)

• Primary Outcome: The primary endpoint of the study will be an absolute change of maxLCBI(4mm) between baseline and 36-week follow-up.

Secondary Outcome

1) Change of atherosclerotic plaque characteristics: evaluate the change of value and rate between baseline and 9M follow up time
Evaluation of NIRS-IVUS data
LCBI(lesion), Angle of lipid core, EEM(External elastic membrane), CSA(Cross-sectional area),
Lumen CSA, Minimum lumen diameter, Plaque burden, Lesion length, TAV(Total atheroma volume), PAV(Percent atheroma volume)
Evaluation of the blood sample
Value of change about low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), non high-density lipoprotein cholesterol, Apolipoproteins, Lipoprotein (a) (Lp (a)), remnant like particles-cholesterol, CRP
Evaluation of residual serum sample
Value of change about cholesterol uptake capacity of HDL, fatty acid profile, ApoB-48, interleukin 1beta(IL1beta), fibroblast glowth factor 21

2) Safety assessment
The safety of pemafibrate including the expression of cardiovascular events (coronary artery disease death, nonfatal myocardial infarction, lethal/nonfatal cerebral infarction, and unstable angina requiring hospitalization)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who satisfy all of the following inclusion criteria were enrolled in this study.
(1)Patients who underwent PCI with ACS (ST-elevated myocardial infarction, non-ST elevated myocardial infarction, unstable angina) or stable angina pectoris
ACS definition:
A) ST-elevated myocardial infarction
(1) Chest symptoms (chest pain, shortness of breath, etc.) suggestive of ischemia are observed.
(2) ST elevation of 1 mm or more in two or more successive chest leads or limb lead electrocardiograms, or new onset left bundle branch block was detected
(3) Increasing of blood test value suggesting myocardial necrosis (troponin T or troponin I is positive, or CPK is more than twice the upper limit of the reference value).

B) Non-ST elevated myocardial infarction
(1) Chest symptoms (chest pain, shortness of breath, etc.) suggestive of ischemia are observed.
(2) ST depression more than 0.5 mm, negative T wave (3 mm or more, or transient ST rise (0.5 mm or less) is detected.
(3) Increasing of blood test value suggesting myocardial necrosis (troponin T or troponin I is positive, or CPK is more than twice the upper limit of the reference value).

C) Unstable angina: It is defined as satisfying (1) and satisfying any one of (2) to (6).
(1) Chest symptoms (chest pain, shortness of breath, etc.) suggestive of ischemia are observed.
(2) ST depression of 0.5 mm or more, or T wave deformation of 3 mm or more is observed.
(3) Increasing of troponin T is observed.
(4) Confirm by diagnostic imaging of culprit lesions of ACS (CAG, MDCT, etc.).
(5) A new wall motion reduction is observed by echocardiography.
(6) There is reversible myocardial blood flow reduction induced by a drug, exercise load, or thallium scintigraphy.

D) sAP: sAP does not fall under any of the above, but satisfies one of the following (1) to (3).
(1) There are symptoms suggestive of ischemia.
(2) There is reversible myocardial blood flow reduction induced by a drug, exercise load, or thallium scintigraphy.
(3) There is significant stenosis in a coronary artery with image diagnosis (CAG, MDCT, etc.).

(2)Patient who received statin therapy before PCI or statin therapy started after PCI.
(3)At the time of PCI, 25 to 75% of non-treated lesions remained, patients with images of analyzable NIRS-IVUS and maxLCBI (4 mm)>100.
(4)Patients who had a fasting TG level of 150 mg/dl or higher or a non-fasting TG level of 175 mg/dl or higher before randomization.
(5)Patients with <100 mg/dl of LDL-C at the time of randomization.(<70 mg/dl of LDL-C for patients who have past history of ACS or with familial hypercholesterolemia, or diabetic patients who are complicated by noncardiogenic cerebral infarction, peripheral arterial disease, metabolic syndrome, multiple majo risk factors or smoking)
(6)Patients aged 20 years or older at the time of PCI.
(7)Patient who got written informed consent from himself or herself.

Exclude criteria

Patients who satisfy any of the following exclusion criteria were excluded from this study.
(1) Patients who have been treated with fibrates before PCI.
(2) Patients had uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) between the time of PCI and randomization visit.
(3) Patients who have a HbA1c level of 7.0 % or higher despite treatment.
(4) Patients who known hypersensitivity to pemafibrate or rosuvastatin.
(5) Patients with severe liver or renal dysfunction.
(6) Patients with any of the warnings, contraindications mentioned in the domestic package insert of rosuvastatin.
(7) Patients with any of the warnings, contraindications mentioned in the domestic package insert of pemafibrate.
(8) Pregnant or breast-feeding women.
(9) Patients recognized as inadequate by attending physician

Related Information

• Primary Sponsor: Toh Ryuji