Impact of PCSK9 Inhibitors on Coronary Plaque Composition and Vulnerability Assessed by Optical Coherence Tomography

NCT ID: NCT04851769

Last Updated: 2021-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-02
• Study Completion Date: 2021-03-01

Brief Summary

The study is a prospective, open-label, randomized, single-center study involving patients with intermediate coronary lesions (50%-70% diameter stenosis) and who have elevated LDL-C values (LDL-C≥100 mg/dL) despite stable statin therapy.

Eligible patients are randomized to receive either alirocumab or standard-of-care (1:1). The last dose of alirocumab will be given at week 34. Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day). Patients in the standard-of-care arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. OCT images will be acquired at the baseline and at week 36 ± 2 weeks follow-up.

Detailed Description

The study is a prospective, open-label, randomized, single-center study involving patients with intermediate coronary lesions (50%-70% diameter stenosis) and who have elevated LDL-C values (LDL-C≥100 mg/dL) despite stable statin therapy.

Eligible patients included those who are (I) at least 18 years of age, (II) diagnosed as stable coronary artery disease or acute coronary syndrome during admission (III) undergoing clinically indicated coronary angiography and identified with at least one intermediate lesion (50%-70% diameter stenosis) on de novo coronary arteries, (IV) have an elevated LDL-C values (LDL-C≥100 mg/dL) despite taken rosuvastatin 10 mg/day or atorvastatin 20 mg/day for 2-4 weeks after initiation or with maximally tolerated statin therapy, (V) able to provide written, informed consent.

The study included a 36-week open-label treatment period (including post-treatment OCT imaging), starting within 4 weeks of baseline coronary angiogram. During the open-label treatment period, patients are randomized to receive either alirocumab or standard-of-care (1:1). The last dose of alirocumab will be given at week 34.

Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day). Patients in the standard-of-care arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. Statin dose escalation or adding concomitant non-statin lipid-lowering therapy would be considered by their responsible physician to achieve an LDL-C target <100 mg/dL. Antithrombotic therapy and other concomitant medications are exclusively decided by the responsible physicians. Follow-up coronary angiograms and OCT imaging analyses of the same vessels will be carried out at the end of treatment period (at week 36 ± 2 weeks, depending on patient availability) in both study arms. Regular medical examination and laboratory tests will be conducted at weeks 4, 12, 24, and 36. All enrolled patients are monitored and evaluated for safety and any other adverse events during the study period.

Conditions

Randomized Controlled Trials

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

alirocumab plus statin

Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).

Group Type: EXPERIMENTAL

PCSK9 inhibitor plus statin

Intervention Type: DRUG

Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).

Coronary imaging follow-up

Intervention Type: PROCEDURE

coronary angiography and OCT imaging at week 36 ± 2 weeks follow-up

standard statin therapy

Patients in the standard statin arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. Statin dose escalation or adding concomitant non-statin lipid-lowering therapy could be considered by their responsible physician to achieve an LDL-C target \<100 mg/dL.

Group Type: ACTIVE_COMPARATOR

standard statin therapy

Intervention Type: DRUG

Patients will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day.

Coronary imaging follow-up

Intervention Type: PROCEDURE

coronary angiography and OCT imaging at week 36 ± 2 weeks follow-up

Interventions

PCSK9 inhibitor plus statin

Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).

Intervention Type: DRUG

standard statin therapy

Patients will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day.

Intervention Type: DRUG

Coronary imaging follow-up

coronary angiography and OCT imaging at week 36 ± 2 weeks follow-up

Intervention Type: PROCEDURE

Other Intervention Names

alirocumab

Eligibility Criteria

Inclusion Criteria

(I) 18 - 80 years of age, (II) diagnosed as stable coronary artery disease or acute coronary syndrome during admission (III) undergoing clinically indicated coronary angiography and identified with at least one intermediate lesion (50%-70% diameter stenosis) on de novo coronary arteries, (IV) have an elevated LDL-C values (LDL-C≥100 mg/dL) despite taken rosuvastatin 10 mg/day or atorvastatin 20 mg/day for 2-4 weeks after initiation or with maximally tolerated statin therapy, (V) able to provide written, informed consent.

Exclusion Criteria

1. Patients who have been treated previously with at least one dose of any anti-PCSK9 monoclonal antibody

2. received target vessel revascularization

3. Known hypersensitivity or have contraindications to any anti-PCSK9 monoclonal antibody or statins

4. Unable to receive OCT imaging tests

5. Known history of hemorrhagic stroke

6. Currently under treatment for cancer

7. Baseline triglyceride > 400 mg/dl

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Anzhen Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yujie Zhou

Vice president, professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yujie Zhou, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Anzhen Hospital

Locations

Beijing Anzhen Hospital

Beijing, Beijing Municipality, China

Countries

China

References

Gao F, Li YP, Ma XT, Wang ZJ, Shi DM, Zhou YJ. Effect of Alirocumab on Coronary Calcification in Patients With Coronary Artery Disease. Front Cardiovasc Med. 2022 May 6;9:907662. doi: 10.3389/fcvm.2022.907662. eCollection 2022.

Reference Type: DERIVED

PMID: 35600486 (View on PubMed)

Gao F, Wang ZJ, Ma XT, Shen H, Yang LX, Zhou YJ. Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography. Lipids Health Dis. 2021 Sep 12;20(1):106. doi: 10.1186/s12944-021-01528-3.

Reference Type: DERIVED

PMID: 34511134 (View on PubMed)

Other Identifiers

anzhen201803

Identifier Type: -

Identifier Source: org_study_id