TRial of Atorvastatin for the primary prevention of Cardiovascular Events in Rheumatoid Arthritis

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 3002

Inclusion Criteria

Current inclusion criteria as of 30/04/2008:
1. Patients must satisfy the 1987 ACR criteria for rheumatoid arthritis applied cumulatively
2. Patients must be aged more than 50 or have had RA disease duration for more than 10 years
3. Patients must provide their written informed consent

Previous inclusion criteria:
1. Patients must satisfy the 1987 ACR criteria for rheumatoid arthritis applied cumulatively
2. Patients must be 40 years or older
3. Patients must provide their written informed consent

Exclusion Criteria

Current exclusion criteria as of 30/04/2008:
1. Patients who are pregnant or women of child-bearing age not using adequate contraception
2. Known primary muscle disorder
3. Known atherosclerotic disease
4. Known familial hyperlipidamia requiring drug therapy
5. Known diabetes
6. Known hypersensitivity or intolerance to statins
7. Active liver disease or hepatic dysfunction with Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) more than two times Upper Limit of Normal (ULN)
8. Severe renal dysfunction (creatinine >150 micromol/l)
9. Creatinine phosphokinase (CK) more than three times ULN
10. Uncontrolled hypothyroidism (defined as any elevation of Thyroid-Stimulating Hormone [TSH] above ULN)
11. Participation in another clinical trial concurrently or within 30 days prior to screening for entry into this study (patients may be participating in an observational study such as the British Society for Rheumatology Biologics register)
12. Other serious illness or significant abnormalities that may compromise the patient's safety or successul participation in the study
13. Any illness which, in the doctor's opinion, means that the patient is unable to give informed consent
14. Known alcohol abuse

Previous exclusion criteria:
1. Patients who are pregnant or women of child-bearing age not using adequate contraception
2. Known primary muscle disorder
3. Known atherosclerotic disease
4. Known familial hyperlipidamia requiring drug therapy
5. Known diabetes
6. Calculated absolute ten year Cardio-Vascular Disease (CVD) risk of 20% or higher, using the Joint British Societies revised risk calculator
7. Known hypersensitivity or intolerance to statins
8. Active liver disease or hepatic dysfunction with Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) more than two times Upper Limit of Normal (ULN)
9. Severe renal dysfunction (creatinine >150 micromol/l)
10. Creatinine phosphokinase (CK) more than three times ULN
11. Uncontrolled hypothyroidism (defined as any elevation of Thyroid-Stimulating Hormone [TSH] above ULN)
12. Participation in another clinical trial concurrently or within 30 days prior to screening for entry into this study (patients may be participating in an observational study such as the British Society for Rheumatology Biologics register)
13. Other serious illness or significant abnormalities that may compromise the patient's safety or successul participation in the study
14. Any illness which, in the doctor's opinion, means that the patient is unable to give informed consent
15. Known alcohol abuse

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Cardiovascular primary endpoint for all patients: all cardiovascular events (analysed by time to FIRST event) briefly defined as: fatal myocardial infarction, other acute coronary heart disease death, definite or probable hospital-verified non-fatal acute myocardial infarction, resuscitated cardiac arrest, definite silent myocardial infarction verified by an electrocardiogram (ECG), coronary revascularisation procedures, hospital admission for acute coronary syndrome, fatal stroke or peripheral arterial event (using predefined standard definitions) and hospital-verified non-fatal stroke or peripheral atherosclerotic events. The endpoints assessment committee will adjudicate this.<br><br> Rheumatology primary outcome (disease activity substudy only): Disease Activity Score 28 (DAS28) at six months, response will be judged using the European League Against Rheumatism (EULAR) response criteria.<br>

Secondary Outcome Measures

Name	Time	Method
<br> Secondary endpoints for all patients:<br> 1. All-cause mortality<br> 2. Changes in fasting lipids and C-Reactive Protein (CRP)<br> 3. Functional outcome (assessed by the Health Assessment Questionnaire [HAQ] and EuroQoL instrument [EQ5D])<br> 4. Statin safety-related outcomes.<br><br> Rheumatology secondary outcomes (disease activity substudy only): Disease-Modifying Anti-Rheumatic Drug (DMARD) changes, DAS28 at years one, two and five.<br><br> Not applicable as of 30/04/2008:<br> Radiological outcome (assessed by the Larsen score in X-rays of hands and wrists - only at year two.<br>

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