Effect of PEMAfibrate on COronary plaques and REnal function in patients with cardiovascular disease and elevated fasting triglyceride

JRCT ID: jRCTs031210067

Registered date:06/05/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Coronary artery disease; ACS, Stable angina, SMI
• Date of first enrollment: 29/06/2021
• Target sample size: 300
• Countries of recruitment: N A,Japan
• Study type: Interventional

Intervention(s)

Pemafibrate group:
Subjects administer 0.2mg of pemafibrate orally twice in a day (morning and evening).
Statins or other antidyslipidemia agents which are used at giving their consent are continuously used till week 72 without change the types, dose, and usage after the allocation.

Control group:
Statins or other antidyslipidemia agents which are used at giving their consent are continuously used till week 72 without change the types, dose, and usage after the allocation.

Outcome(s)

Primary Outcome

1) Percent change in volume of the target plaque to be analyzed in this study, which is not treated by PCI in the longitudinal 10mm segment from baseline to week 72
2) Change in LCBImax4mm assessed by NIRS at the target plaque to be analyzed in this study, which is not treated by PCI from baseline to week 72

Secondary Outcome

[Endpoints in coronary artery plaque]
Following items at the target plaque to be analyzed in this study or the coronary artery with thetarget plaque to be analyzed in this study from baseline to week 72
1) change in LCBI assessed by NIRS
2) change in percent atheroma volume
3) change in plaque volume
4) percent change in plaque volume (< 0%)
5) change in plaque percent atheroma volume (< 0)
6) change in LCBImax4mm (< 0)
7) change in LCBI (< 0)
8) change in calcification score
9) percent change in remodeling coefficient
10) change in attenuation score by echogenicity in the plaque
11) change in luminal volume

[Endpoints in renal function (catheter-related acute renal dysfunction)]
1) measurements, change and percent change in the following 5 items before the coronary angiography upon PCI to the next day at baseline
2) measurements, change and percent change in the following 5 items before the coronary angiography to the next day at week 72
i) urine NGAL/creatinine ratio and urine NGAL concentration
ii) urine albumin/creatinine ratio
iii) Blood level of cystatin C
iv) Serum creatinine
v) eGFR (eGFRcreat and eGFRcys)
3) Number of acute tubular disorder, defined as urine NGAL of more than 99.0ng/mL, at the next day of the coronary angiography at baseline and week 72

[Endpoints in renal function (chronic renal dysfunction)]
1) frequency of renal event (following composite events)
i) increase of serum creatinine twice or more from baseline
ii) progression to end-stage renal failure (eGFR is less than 15 mL/min/1.73m2) or introduction of maintenance dialysis
iii) decrease of eGFR 30% or more from baseline (if eGFRcreat is less than 60 mL/min/1.73m2)

[Outcome indicators]
1) Frequency of major adverse cardiovascular events (following 4 composite events)
- cardiac death, non-fatal myocardial infarction, non-fatal ischemic stroke, and hospitalization due to unstable angina requiring revascularization
2) Frequency of cardiac death
3) Frequency of non-fatal myocardial infarction
4) Frequency of non-fatal ischemic stroke
5) Frequency of hospitalization due to unstable angina requiring revascularization
6) Frequency of revascularization
7) Frequency of hospitalization due to heart failure
8) Frequency of peripheral arterial disease
9) Total mortality

[Safety endpoints]
1) Number and Frequency of adverse events and disease or the like occurred during the study period

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 85age old
• Gender: Both

Include criteria

<at provisional registration>
1) male and female aged 20 years or older and younger than 85 years at giving their consent
2) Patients with coronary artery disease, which meets the medical indication of percutaneous coronary intervention (PCI), or patients with suspected coronary artery disease, which meets the medical indication of coronary angiography, according to the JCS 2018 Guideline on Diagnosis of Chronic Coronary Heart Diseases, the JCS 2018 Guideline on Revascularization of Stable Coronary Artery Disease, or the JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome, released by the Japanese Circulation Society.
3) Patients who have used statin continuously 180 days or longer before the planned day of the PCI (regardless of types, dose, or changes of statins).
4) Patients whose LDL-c under the treatment with statin became less than 100mg/dL at least once within 60 days before the planned day of the PCI.
5) Patients whose fasting triglyceride under the treatment with statin became 150mg/dL or higher and less than 500mg/dL at least once within 60 days before the planned day of the PCI.
6) Patients who provide their consent to participate in this study in a written form by themselves.

<at actual registration>
Provisionally-registered patients who meet all of the following inclusion criteria and do not fall into any of exclusion criteria are actually registered, based on the findings by the coronary angiography and coronary imaging at the time of PCI, the success or failure of the PCI, and the status of statin administration. If the provisionally-registered patients are judged to be ineligible at this time, the patients are not registered.
1) Patients in whom the PCI procedure at the culprit lesion of the coronary artery disease was succeeded.
2) Patients who have another coronary lesion which is less than 75% by AHA lesion classification at proximal or distal portion apart from the PCI-treated lesion 5mm or more, or patients who have another coronary lesion which is less than 75% by AHA lesion classification at different coronary artery branches from the PCI-treated lesion.
3) Patients who have used statin continuously 180 days or longer before the actual registration.

Exclude criteria

<at provisional registration>
1) Patients with heart failure (class III or IV by NYHA classification)
2) Patients with poorly-controlled hypertension (systolic blood pressure is 200mmHg or higher, or diastolic blood pressure is 110mmHg or higher) regardless of antihypertensive agents administration
3) Patients with poorly-controlled diabetes mellitus (HbA1c is 9.5% or higher)
4) Patients with hepatic dysfunction (ALT or AST is 2.5 fold or more higher than the upper limit of normal)
5) Patients with hepatic cirrhosis (Child-Pugh class B or C)
6) Patients with gallstone or biliary obstruction
7) Patients with renal dysfunction (serum creatinine is 1.5mg/dL or higher) or patients who are treated by dialysis.
8) Patients who are using any fibrates, PCSK9 inhibitors, EPAs, or EPA/DHAs.
9) Patients who are breastfeeding, pregnant, or possibly pregnant.
10) Patients who are using cyclosporine or rifampicin.
11) Patients who have history of hypersensitivity against pemafibrate.
12) Patients who are participating other clinical studies.
13) Patients with other conditions that the responsible investigator or subinvestigators think inappropriate to participate in the study.

<at actual registration>
1) Patients who have history of PCI at the target plaque to be analyzed in this study confirmed by the intravascular ultrasonography.
2) Patients who may undergo another PCI in the same vessel as the target plaque to be analyzed in this study confirmed by the intravascular ultrasonography during the study period.
3) Patients with significant calcification confirmed by coronary angiography in the coronary artery with the target plaque to be analyzed in this study, which may make NIRS/IVUS and OCT difficult in the vessel.
4) Patients with significant bending confirmed by coronary angiography in the coronary artery with the target plaque to be analyzed in this study, which may make NIRS/IVUS and OCT difficult in the vessel.
5) Patients who are expected to be treated with coronary artery bypass graft surgery during the study period
6) Patients with other conditions that the responsible investigator or subinvestigators think inappropriate to participate in the study.

Related Information

• Primary Sponsor: Yasuda Satoshi
• Source(s) of Monetary Support: Kowa Company, Ltd.,Nipro Corporation