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

1. To evaluate the prevalence of preclinical atherosclerosis in Chinese patients with RA compared to healthy controls.

2. To determine those clinical and biological measures that best predict the presence of plaque and increased arterial stiffness.

3. To ascertain the efficacy and safety of rosuvastatin in the prevention of atherosclerosis in patients with RA measured by carotid intima-media thickness and pulse wave velocity.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Rosuvastatin
  • 5mg daily for 4 weeks then step up to 10mg or matching placebo for 52 weeks
• Drug: Placebo
  • 5mg daily for 4 weeks then step up to 10mg or matching placebo for 52 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Rosuvastatin
• Placebo Comparator: 2
  • Placebo

Primary Measures

• Improvement of atherosclerosis by Rosuvastatin therapy, evaluated by IMT and PWV.
  • Time Frame: baseline,wk24,wk52
    Safety Issue?: Yes

Secondary Measures

• 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.
  • Time Frame: baseline,wk0,wk3,wk8,wk12,wk24,wk36,wk52
    Safety Issue?: Yes

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≥270µmol/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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Chinese University of Hong Kong

Overall Clinical Trial Officials and Contacts

Edmund Kwok Ming Li, MD Principal Investigator Chinese University of Hong Kong  

Overall Contact: Lai-Shan Tam, MD (852)2632-3173 lstam@cuhk.edu.hk

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00555230

Study ID Number: RA-2007-004

ClinicalTrials.gov Identifier: NCT00555230

Health Authority: Hong Kong: Department of Health