The Efficacy of Alirocumab for Thin-cap fIbroatheroma in Patients With Coronary Artery Disease Estimated by Optical Coherence Tomography (ALTAIR)

The Efficacy of Alirocumab for Thin-cap fIbroatheroma in Patients With Coronary Artery Disease Estimated by Optical Coherence Tomography: Single Center, Randomized, Open-label, Trial

the purpose of this study is to show that alirocumab with statin therapy have a s tronger stabilizing effect on vulnerable plaque in coronary artery disease than statin alone administration

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Thin-cap fIbroatheroma
• Intervention / Treatment: Drug: Alirocumab

Detailed Description

The investigators investigate to evaluate the efficacy of alirocumab for vulnerable plaque. The investigators enrolled the patient with standard statin therapy who were detected vulnerable plaque by optical coherence tomography, and categorized into two group; the patients with alirocumab and rosuvastatin were categorized alirocumab therapy group, and the patients with rosuvastatin alone were categorized standard statin therapy group. The investigators compare these two group for outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hiromasa Otake, M.D, Ph,D; Phone Number: +81-78-382-5846; Email: hotake@med.kobe-u.ac.jp

Study Locations

• Japan
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0017
      • Recruiting
      • Kobe University Graduate School of Medicine, Department of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who underwent PCI for ACS or stable coronary heart disease
2. Patients with LDL-C ≥70 mg/dL under daily 10mg rosuvastatin
3. Patients who have been had TCFA detected by OCT
4. Patients aged ≥20 years old at PCI
5. Patients who agree to be enrolled in the trial giving signed written informed consent

Exclusion 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. Known hypersensitivity to alirocumab or rosuvastatin
4. All contraindications to alirocumab and/or rosuvastatin as displayed in the respective national product labeling for these treatments
5. Known history of hemorrhagic stroke
6. Currently under treatment for cancer
7. Patients on lipoprotein apheresis
8. Patients with severe liver or renal dysfunction
9. Pregnant or breast-feeding women
10. Considered by the investigator as inappropriate for this study for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alirocumab therapy group; start with alirocumab 75mg per 2weeks and rosuvastatin 10mg per day	Drug: Alirocumab; the administration of Alirocumab by Subcutaneous injection 75mg every 2 weeks plus Rosuvastatin10mg/daily by oral for 9 months
No Intervention: standard statin therapy group; start with only rosuvastatin 10mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change in fibrous cap thickness	the absolute change in minimum fibrous-cap thickness between baseline and 36-week follow-up	9 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change in fibrous cap thickness	the percent change in minimum fibrous-cap thickness between baseline and 36-week follow-up	9 month
the change in lipid index	absolute change in lipid index between baseline and 36-week follow-up	9 month
the change in lipid index	percentage change in lipid index between baseline and 36-week follow-up	9 month
the change in lipid length,	absolute change in lipid core length between baseline and 36-week follow-up	9 month
the change in lipid length,	percentage change in lipid core length between baseline and 36-week follow-up	9 month
the change in mean lipid arc	absolute change in mean lipid arc between baseline and 36-week follow-up	9 month
the change in mean lipid arc	percentage change in mean lipid arc between baseline and 36-week follow-up	9 month
the change in max lipid arc	absolute change in max lipid arc between baseline and 36-week follow-up	9 month
the change in max lipid arc	percent change in max lipid arc between baseline and 36-week follow-up	9 month
the change in macrophage grade	absolute change in summation of macrophage grade between baseline and 36-week follow-up. macrophage grade defined as an OCT macrophage grading system to semiquantify the bright spots based on axial and circumferential distribution, as follows: grade 0, no macrophage; grade 1, localized macrophage accumulation; grade 2, clustered accumulation <1 quadrant; grade 3, clustered accumulation >1 quadrant and ≦3 quadrants; and grade 4, clustered accumulation ≧3	9 month
the change in macrophage grade	percentage change in summation of macrophage grade between baseline and 36-week follow-up. macrophage grade defined as an OCT macrophage grading system to semiquantify the bright spots based on axial and circumferential distribution, as follows: grade 0, no macrophage; grade 1, localized macrophage accumulation; grade 2, clustered accumulation <1 quadrant; grade 3, clustered accumulation >1 quadrant and ≦3 quadrants; and grade 4, clustered accumulation ≧3	9 month
the change in minimum lumen area	absolute change in minimum lumen area between baseline and 36-week follow-up	9 month
the change in minimum lumen area	percentage of change in minimum lumen area between baseline and 36-week follow-up	9 month
the number of thin-cap fibroatheroma	change of the number of thin-cap fibroatheroma at 36-week follow-up	9 month
the change in total cholesterol	absolute change in serum level of of total cholesterol between baseline and 36-week follow-up	9 month
the change in total cholesterol	percent change in serum level of of total cholesterol between baseline and 36-week follow-up	9 month
the change in LDL-C	absolute change in serum level of of LDL-C between baseline and 36-week follow-up	9 month
the change in LDL-C	percentage change in serum level of of LDL-C between baseline and 36-week follow-up	9 month
the change in HDL-C	absolute change in serum level of of HDL-C between baseline and 36-week follow-up	9 month
the change in HDL-C	percentage change in serum level of of HDL-C between baseline and 36-week follow-up	9 month
the change in non-HDL-C	absolute change in serum level of of non-HDL-C between baseline and 36-week follow-up	9 month
the change in non-HDL-C	percentage change in serum level of of non-HDL-C between baseline and 36-week follow-up	9 month
the change in apolipoprotein B	absolute change in serum level of of apolipoprotein B between baseline and 36-week follow-up	9 month
the change in apolipoprotein B	percentage change in serum level of of apolipoprotein B between baseline and 36-week follow-up	9 month
the change in Lp(a)	absolute change in serum level of of Lp (a) between baseline and 36-week follow-up	9 month
the change in Lp(a)	percentage change in serum level of of Lp (a) between baseline and 36-week follow-up	9 month
the change in hs-CRP	absolute change in serum level of hs-CRP between baseline and 36-week follow-up	9 month
the change in hs-CRP	percentage change in serum level of hs-CRP between baseline and 36-week follow-up	9 month
the change in IL-1β	absolute change in serum level of IL-1β between baseline and 36-week follow-up	9 month
the change in IL-1β	percentage change in serum level of IL-1β between baseline and 36-week follow-up	9 month
the change in IL-6	absolute change in serum level of IL-6 between baseline and 36-week follow-up	9 month
the change in IL-6	percentage change in serum level of IL-6 between baseline and 36-week follow-up	9 month
the change in TNF-α	absolute change in serum level of TNF-α between baseline and 36-week follow-up	9 month
the change in TNF-α	percentage change in serum level of TNF-α between baseline and 36-week follow-up	9 month
the change in MCP-1	absolute change in serum level of MCP-1 between baseline and 36-week follow-up	9 month
the change in MCP-1	percentage change in serum level of MCP-1 between baseline and 36-week follow-up	9 month
the change in MMP-2	absolute change in serum level ofMMP-2 between baseline and 36-week follow-up	9 month
the change in MMP-2	percentage change in serum level ofMMP-2 between baseline and 36-week follow-up	9 month
the change in MMP-9	absolute change in serum level of MMP-9 between baseline and 36-week follow-up	9 month
the change in MMP-9	percentage change in serum level of MMP-9 between baseline and 36-week follow-up	9 month
the change in VCAM-1	absolute change in serum level of VCAM-1between baseline and 36-week follow-up	9 month
the change in VCAM-1	percentage change in serum level of VCAM-1 between baseline and 36-week follow-up	9 month
the change in ICAM-1	absolute change in serum level of ICAM-1 between baseline and 36-week follow-up	9 month
the change in ICAM-1	percentage change in serum level of ICAM-1 between baseline and 36-week follow-up	9 month
the change in free PCSK9	absolute change in serum level of free PCSK9 between baseline and 36-week follow-up	9 month
the change in free PCSK9	percentage change in serum level of free PCSK9 between baseline and 36-week follow-up	9 month

Collaborators and Investigators

• Sponsor: Kobe University
• Investigators: Principal Investigator: Hiromasa Otake, M.D, Ph,D, Kobe University Graduate School of Medicine

Publications and helpful links

General Publications

• Otake H, Sugizaki Y, Toba T, Nagano Y, Tsukiyama Y, Yanaka KI, Yamamoto H, Nagasawa A, Onishi H, Takeshige R, Nakano S, Matsuoka Y, Tanimura K, Kawamori H, Shinke T, Hirata KI. Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin. J Cardiol. 2019 Mar;73(3):228-232. doi: 10.1016/j.jjcc.2018.11.012. Epub 2018 Dec 19.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2017
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: May 7, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 11, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Optical Coherence Tomography (OCT); vulnerable plaque; alirocumab; Thin-cap fIbroatheroma (TCFA)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Plaque, Atherosclerotic
• Other Study ID Numbers: KobeU-290017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No