High-Resolution Assessment of Extracranial Plaques in Evolocumab Treatment

Sponsor

Wuhan Union Hospital, China (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05585151

Collaborator

(none)

200

Enrollment

Arms

23.7

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cerebral Atherosclerosis	Drug: Evolocumab 140 MG/ML Drug: Intensive statin treatment	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 12, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Changes of the thickness of minimum fibrous cap of artery plaque measured by OCT [27 Weeks ± 7 days]
Changes of the thickness of minimum fibrous cap of artery plaque measured by OCT

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years old, regardless of sex;
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 V1 segment) was 30%-69%; 2) The target vessel for imaging has not undergone or intends to undergo revascularization and must be available for OCT imaging catheter;
Fasting LDL-C level ≥ 1.8mmol/L;
Participants who understand and sign the informed consent form voluntarily.

Exclusion Criteria:

Intolerant to atorvastatin and Rosuvastatin;
A history of major surgery or endovascular therapy within 3 months before the screening period;
Stenosis or occlusion of arteries not caused by atherosclerosis, such as arterial dissection, Moya-moya disease, vasculitis, radio-vascular disease, or fibromuscular dysplasia;
Abnormal liver function (ALT > 3 times the upper limit of normal value);
Abnormal renal function (eGFR < 45 mL/min/1.73m2);
Thrombocytopenia (PLT < 100G/L);
The life expectancy of the subjects is less than 6 months;
During the screening period, there are known serious life-threatening diseases (e.g., hematological disease, malignancy), unstable vital signs or the need for continuous monitoring or a dying state;
Patients have been included in other studies that conflicts with this study;
Known allergy to any product or ingredient during administration;
Pregnant women, breastfeeding, or trying to become pregnant.
Other conditions considered inappropriate for enrollment by the investigators.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

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