Effects of HMG-coA Reductase Inhibitor on Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is: To evaluate the prevalence of preclinical atherosclerosis in Chinese patients with RA compared to healthy controls. To determine those clinical and biological measures that best predict the presence of plaque and increased arterial stiffness. To ascertain the efficacy and safety of rosuvastatin in the prevention of atherosclerosis in patients with RA measured by carotid intima-media thickness (IMT) and pulse wave velocity (PWV).

Detailed Description
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150 consecutive RA patients followed at the Rheumatology clinic of the Prince of Wales Hospital will be recruited for this double-blind, randomized, placebo-control trial. Patients were matched to 150 controls on the basis of age (within 5 years), sex, body mass index (+/-5Kg) and ethnicity for the cross sectional study on the prevalence of subclinical atherosclerosis. Controls were healthy individuals recruited from the same community who underwent similar imaging protocols of the IMT and PWV assessments. Primary outcome is the improvement of atherosclerosis by Rosuvastatin therapy, evaluated by IMT and PWV. Secondary outcomes: Prevalence of premature atherosclerosis in RA patients compared to healthy controls in terms of the presence of plague and PWV. Correlation between clinical parameters, inflammatory markers (CRP/hsCRP, TNF-alpha and IL-6) and atherosclerosis (evaluated by IMT, the presence of plaque and PWV). Relation among PWV, ABI and AI in RA patients, and clinical significance of their combination. Determine which segment's PWV has a better relation with RA disease activity.

Official Title
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Effects of HMG-coA Reductase Inhibitor on Progression of Carotid Intima-Media Thickness and Arterial Stiffness in Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women, 18 years of age or older Clinical diagnosis of RA with a duration of at least 6 month Prednisolone < =10 mg/day NSAID or DMARD Informed consent Exclusion Criteria: Little or no ability for self-care Type 1 diabetes mellitus Uncontrolled hypertension(> 160/95 mmHg) Total cholesterol > 240 mg/dl, current or recent (within the past 3 months) History of coronary bypass grafting, myocardial infraction within 28days, left ventricular dysfunction (ejection fraction < 40%), significant valvular heart disease Current treatment with ACE inhibitor, angiotensin II receptor blockers or beta-blockers, lipid lowering drug, or contra-indication to statins Current treatment of oral contraceptives, estrogen and progestin was allowed but patient not willing to stop during study Current treatment with antioxidant therapy (Vitamin C or multivitamin) Received intra-articular, intramuscular, or intravenous corticosteroids in the past 4 weeks before screening Clinically significant renal disease(serum creatinine level ≥ 270 µmol/L) or aspartate aminotransferase(AST), alanine aminotransferase ALT), or creatine kinase (CK)≥ 2 X ULN Female of childbearing potential, unwilling to use adequate contraception during the study Current or recent (within the past 3 months) pregnancy and cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Rosuvastatin | Drug: Rosuvastatin<br>* 5mg daily for 4 weeks then step up to 10mg or matching placebo for 52 weeks<br>* Other names: crestor;|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* 5mg daily for 4 weeks then step up to 10mg or matching placebo for 52 weeks<br>* Other names: crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of atherosclerosis by Rosuvastatin therapy, evaluated by IMT and PWV. |  | baseline,week24,week52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| physical examination,blood pressure,pulse rate,and body weight measurements at each visit.Liver function and CK are performed at baseline,week 12,24 and 52.Correlation between clinical parameters,inflammatory markers and atherosclerosis. |  | baseline,week0,week3,week8,week12,week24,week36,week52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HMG-CoA reductase inhibitors, Crestor, Rosuvastatin