High-Resolution Assessment of Extracranial Plaques in a Multiple Centers Evolocumab Randomized Study

This study intends to explore the therapeutic effect of PCSK9i Evolocumab on atherosclerotic plaques in cerebral arteries (including carotid and vertebral arteries) compared with intensive statin treatment, and monitor the pathological properties of carotid/vertebral artery plaques with OCT technology. At the same time, three-dimensional ultrasound and high-resolution magnetic resonance are used to explore the new mechanism of pathological changes of cerebral atherosclerotic plaques in a multidimensional manner.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Atherosclerosis
• Intervention / Treatment: Drug: Evolocumab 140 MG/ML; Drug: Intensive statin treatment

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yan Wan, Doctor; Phone Number: +8615872394527; Email: wanyanalan@163.com
• Study Contact Backup: Name: Shengcai Chen, Doctor

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Yan Wan, PHD; Phone Number: +8615872394527; Email: wanyanalan@163.com
      • Contact: Shengcai Chen, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old, regardless of sex;
2. Cerebrovascular angiography examination was performed, and the imaging characteristics were consistent with: 1) The stenosis degree of internal carotid artery (starting from C1 segment) or vertebral artery (starting from vertebral artery to V4 segment) was 20%-69%; 2) The target vessel for imaging has not undergone or intends to undergo revascularization and must be available for OCT imaging catheter;
3. Participants who understand and sign the informed consent form voluntarily.

Exclusion Criteria:

1. Intolerant to both atorvastatin and rosuvastatin;
2. History of major surgery or endovascular treatment within 3 months prior to the screening period;
3. Arterial stenosis or occlusion not caused by atherosclerosis, such as arterial dissection, moya-moya disease, vasculitis, radiation vascular disease, or fibromuscular dysplasia;
4. Abnormal liver function (ALT > 3 times the upper limit of normal);
5. Renal dysfunction (glomerular filtration rate (eGFR) <45 mL/min/1.73m2 at screening);
6. Thrombocytopenia (PLT<100G/L);
7. The expected survival time is not more than 6 months;
8. Other known serious life-threatening disease (such as hematologic disease, malignancy), unstable vital signs or need for continuous monitoring, or moribund state during screening;
9. Patients have been included in other studies that conflict with this study;
10. Known sensitivity to any of the products or components to be administered during dosing;
11. Pregnant, breastfeeding or planning pregnancy, and other conditions that the investigator considers the patient unsuitable for enrollment;
12. Other conditions that the investigator considered inappropriate for enrollment.

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: Evolocumab treatment group; Evolocumab treatment, 1ml：140mg, every 2 weeks, for 26 weeks	Drug: Evolocumab 140 MG/ML; Evolocumab 140mg, subcutaneous injection, every 2 weeks, for 26 week, total 13 times
Active Comparator: Intensive statin treatment group; Atorvastatin 40mg/day or rosuvastatin 20mg/day, for 26 weeks	Drug: Intensive statin treatment; Intensive statin could choose either Atorvastatin 40mg/day or Rosuvastatin 20mg/day, for 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of the thickness of fibrous cap of artery plaque measured by OCT	Changes of the thickness of fibrous cap of artery plaque measured by OCT	27 Weeks ± 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of the minimum lumen area (MLA) measured by OCT	Changes of the minimum lumen area (MLA) measured by OCT	27 Weeks ± 7 days
Changes of lumen area stenosis measured by OCT	Changes of lumen area stenosis measured by OCT	27 Weeks ± 7 days
Changes of the number of microvessels measured by OCT	Changes of the number of microvessels measured by OCT	27 Weeks ± 7 days
Changes of the presence and extension of macrophages measured by OCT	Changes of the presence and extension of macrophages measured by OCT	27 Weeks ± 7 days
Changes of the calcium aggregation measured by OCT	Changes of the calcium aggregation measured by OCT	27 Weeks ± 7 days
Changes of arterial plaque volume measured by OCT	Changes of arterial plaque volume measured by OCT	27 Weeks ± 7 days
Changes of lipid necrotic core of arterial plaque measured by OCT	Changes of lipid necrotic core of arterial plaque measured by OCT	27 Weeks ± 7 days
Changes of LDL-C levels	Changes of LDL-C levels	27 Weeks ± 7 days
Changes of the thickness of minimum fibrous cap of artery plaque measured by 3D-ultrasound	Changes of the thickness of minimum fibrous cap of artery plaque measured by 3D-ultrasound	27 Weeks ± 7 days
Changes of arterial plaque volume measured by 3D-ultrasound	Changes of arterial plaque volume measured by 3D-ultrasound	27 Weeks ± 7 days
Changes of Lipid necrotic core of arterial plaque measured by 3D-ultrasound	Changes of Lipid necrotic core of arterial plaque measured by 3D-ultrasound	27 Weeks ± 7 days
Changes of the thickness of minimum fibrous cap of artery plaque measured by High resolution magnetic resonance	Changes of the thickness of minimum fibrous cap of artery plaque measured by High resolution magnetic resonance	27 Weeks ± 7 days
Changes of arterial plaque volume measured by High resolution magnetic resonance	Changes of arterial plaque volume measured by High resolution magnetic resonance	27 Weeks ± 7 days
Changes of Lipid necrotic core of arterial plaque measured by High resolution magnetic resonance	Changes of Lipid necrotic core of arterial plaque measured by High resolution magnetic resonance	27 Weeks ± 7 days
Correlation between arterial plaque and new risk factors for cardiovascular and cerebrovascular diseases (serum hsCRP, other markers, etc.)	Correlation between arterial plaque and new risk factors for cardiovascular and cerebrovascular diseases (serum hsCRP, other markers, etc.)	27 Weeks ± 7 days
Changes of the lipid arc of artery plaque measured by OCT	Changes of the lipid arc of artery plaque measured by OCT	27 Weeks ± 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of ischemic vascular events	Occurrence of ischemic vascular events, such as TIA, acute cerebral infarction, acute myocardial infarction, etc.	27 Weeks ± 7 days
Adverse events/serious adverse events	Adverse events/serious adverse events	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Study Chair: Bo Hu, Doctor, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology; Principal Investigator: Candong Hong, Doctor, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology; Principal Investigator: Lei Zhang, Doctor, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology; Principal Investigator: Quanwei He, Doctor, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology; Principal Investigator: Jiehong Wu, Doctor, Union Hospital, Tongji Medical College, Huahzong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 15, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: OCT; atherosclerosis; Evolocumab; plaque burden; High-Resolution assessment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intracranial Arterial Diseases; Atherosclerosis; Intracranial Arteriosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Serine Proteinase Inhibitors; PCSK9 Inhibitors; Evolocumab
• Other Study ID Numbers: HERALD

Drug and device information, study documents

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