A Study to Evaluate the Efficacy and Safety of Rosuvastatin in the Treatment of the Carotid Atherosclerotic Plaques

Study Overview
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Brief Summary
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This is a 2-year, open-label, randomized study to evaluate the efficacy of Rosuvastatin dosing adjustment by LDL-C level compared to that of 5mg maintenance dose in chinese patients with Carotid Atherosclerosis.

Detailed Description
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This will be a 2-year, randomized, open-label, prospective, parallel-group study. It only be held in China-Japan Friendship Hospital. Subjects with Carotid Atherosclerosis Plaques who meet all inclusion and none of the exclusion criteria will be randomized in a 1:1 ratio to receive treatment of rosuvastatin (5 mg, 10mg, 20mg) dosing adjustment by LDL-c level or fixed dose 5 mg. The study will consist of two phases: the Screening/Baseline period（-1to week 0）and the Follow-up period(0 to month 24). The follow-up period will comprise seven visits.

Official Title
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A 2-year, Open-label, Randomized Study to Evaluate the Efficacy of Rosuvastatin Dosing Adjustment by LDL-C Level Compared to That of 5mg Maintenance Dose in Chinese Patients With Carotid Atherosclerotic Plaques

Conditions
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Carotid Atherosclerosis

Intervention / Treatment
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* Drug: Rosuvastatin (5mg，10mg，20mg)
* Drug: Rosuvastatin 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects or legal guardian can understand and sign the written informed consent form; LDL-C≥100mg/dl（2.6mmol/l）. Subjects with carotid atherosclerotic non-calcified plaques determined by color Doppler ultrasound on carotid. ( Plaque defined as limited intima media thickness≥1.5mm, according to the procedure of vascular ultrasound examination in 2009 Chinese Journal of Ultrasonography ) Subjects had not been treated with statins, or one had been treated with antihyperlipidemics no more than 3 months within 12 months prior to screening. Exclusion Criteria: Subjects known to be allergic to the study medication, or any components . Uncontrolled hypothyroidism defined as the systolic blood pressure(SBP) >180 mmHg or the diastolic blood pressure(DBP) >100 mmHg. Concomitant with severe or frequent arrhythmia, such as Atrial Fibrillation, second or third degree Atrioventricular Block, Sick sinus Syndrome etc. Alanine aminotransaminase (ALT) and /or Aspartate aminotransferase (AST) >1.5×ULN (upper limit of normal). Subjects with myopathies，or the value of Creatine kinase >1.5×ULN (upper limit of normal). Concomitant with chronic wasting diseases, whose life span was anticipated no longer than 2 years. Pregnant or nursing woman, and subjects with a Pregnant plan during this study. Cognitive impairment, which may affect obtaining informed consent and participating in the study procedures. Unwilling to receive treatment or examinations outlined in protocol.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin dose adjustment<br> | Drug: Rosuvastatin (5mg，10mg，20mg)<br>* Rosuvastatin dose adjusted by LDL-c level( If LDL-C>1.1mmol/L and <1.8mmol/L, administrated as 5mg/day.If LDL-C ≥1.8mmol/L, adjusted every 4 weeks as 5mg，10mg，20mg.<br>|
| Experimental: Rosuvastatin fixed dose<br> | Drug: Rosuvastatin 5mg<br>* Rosuvastatin 5mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Carotid Plaque Area | A comparison of the change in total Carotid Plaques area from the two treatment groups examined by color Doppler ultrasound. | Up to 24 months | 
| Total Carotid Plaque Area | Reversal of total Carotid Atherosclerosis Plaques in the two rosuvastatin dose group at 12 months. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Carotid Plaque Area | Changes from baseline in total Carotid Atherosclerosis Plaques (TPA) from the two rosuvastatin treatment groups from baseline at 12 months and 24 months. | Baseline to 12 months and 24 months | 
| Carotid Intima-Media Thickness(IMT) | Changes of Carotid Intima-Media Thickness (IMT) in the two rosuvastatin treatment groups from baseline to 12 months and to 24 months. | Baseline to 12 months and 24 months | 
| The level of Blood lipid | Changes from baseline in the level of Blood lipid from the two rosuvastatin treatment groups. | baseline and 1, 2, 3, 6, 12, 18, 24 months post-dose | 
| Low density lipoprotein-cholesterol (LDL-c) | Analysis of the corrlation between LDL-c and TPA from the two rosuvastatin treatment groups. | Baseline to 12 months and 24 months | 
| Carotid Intima-Media Thickness(IMT) | Analysis of the corrlation between IMT and TPA in each treatment group. | Up to 24 months | 
| Incidence of Adverse Events | The categories and incidences of Adverse Events from the two treatment groups. | Baseline to 24 months | 
| Incidences of Major Adverse Cardiovascular and Cerebrovascular Events（MACCE） | Incidences of Major adverse cardiovascular and cerebrovascular events from the two rosuvastatin treatment groups. | Baseline to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rosuvastatin, Carotid Atherosclerosis plaque, Crestor, Rosuvastatin calcium