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

JRCT ID: jRCT1051180064

Registered date:14/02/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: coronary artery disease
• Date of first enrollment: 26/04/2018
• Target sample size: 30
• Study type: Interventional
• Intervention(s): Patients in the alirocumab arm will receive subcutaneous alirocumab 75 mg every 2 weeks (Q2W) in addition to statin therapy (rosuvastatin 10 mg/day). Patients in the standard-of-care arm will receive rosuvastatin 10 mg/day, with initiation and/or dose adjustment of non-statin lipid-lowering drugs to achieve an LDL-C target <70 mg/dL

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

Secondary outcomes of this study (below)
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 CSA, Lumen CSA, Minimum lumen diameter, Plaque burden, Lesion length
Evaluation of the blood sample
Value of change about high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo-B), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), none high-density lipoprotein cholesterol Lipoprotein (a) (Lp (a)), CRP
Evaluation of residual serum sample
Value of change about Serum PCSK9, TNF-a, IL-6, MCP-1, MMP-2, MMP-9, CAM-1, VCAM-1

2) Safety assessment
The safety of alirocumab 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 and exclusion criteria were enrolled in this study.
Inclusion criteria:
01: 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.).

02: Patient who received statin therapy before PCI or statin therapy started after PCI. Alirocumab is also indicated for familial cholesterolemia or hypercholesterolemia. In this case, since it is an adaptation condition that the control is insufficient with HMG-CoA reductase (statin), the following exclusion criteria (LDL-C <70 mg/dl) are provided and within the scope of the insurance indication in Japan Conformed to usage in.

03: 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.
04: Patients aged 20 years or older at the time of PCI.
05: Patient who got written informed consent from himself or herself.

Exclude criteria

1) Patients who have been treated previously with at least one dose of any anti-PCSK9 monoclonal antibody
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 with <70 mg/dl of LDL-C value
4) Patients who known hypersensitivity to alirocumab or rosuvastatin
5) Patients who know the history of hemorrhagic stroke
6) Patients who received currently under treatment for cancer
7) Patients who received lipoprotein apheresis
8) Patients with severe liver or renal dysfunction
9) Patients with any of the warnings, contraindications mentioned in the domestic package insert of rosuvastatin
10) Patients with any of the warnings, contraindications mentioned in the domestic package insert of alirocumab
11) Pregnant or breast-feeding women
12) Patients recognized as inadequate by attending physician

Related Information

• Primary Sponsor: Otake Hiromasa
• Secondary ID(s): UMIN000031243