SEARCH: Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine - Article
Clinical Trial: SEARCH: Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine
This study is no longer recruiting patients.
|Cardiovascular Disease || Drug: Simvastatin (20mg versus 80mg daily) |
Drug: Folic acid 2mg + vitamin B12 1mg daily
|Phase III |
MedlinePlus related topics: Heart Diseases; Vascular Diseases
Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind, Dose Comparison, Factorial Assignment, Safety/Efficacy Study
Secondary Outcomes: MVEs separately in year 1 and in later years; MVEs in patients subdivided into 3 groups by baseline low-density lipoprotein (LDL); MVEs in presence and absence of the other factorial treatment; Major coronary events; Total strokes
Expected Total Enrollment: 12064
Study start: July 1998
In observational studies, lower blood cholesterol concentrations are associated with lower coronary risk, without any clear threshold below which lower levels are not associated with lower risk. Cholesterol reduction with statins reduces such risk but there is uncertainty about whether greater reductions with more intensive statin therapy will produce greater benefits. Elevated blood homocysteine levels appear to be an independent marker of cardiovascular risk, but it is unknown whether taking vitamins to reduce homocysteine concentrations will translate into cardiovascular benefit.
12,064 survivors of myocardial infarction have been randomised in a 2x2 factorial design to more intensive versus standard cholesterol-lowering treatment, using 80mg or 20mg daily simvastatin, and separately to homocysteine-lowering with folic acid plus vitamin B12 or matching placebo. Follow-up will continue until there are at least 2800 confirmed major vascular events (MVE), defined as non-fatal myocardial infarction, coronary death, stroke or arterial revascularisation. The primary outcome is the incidence of first MVE during the scheduled treatment period.
SEARCH should provide reliable evidence of the effectiveness and safety of more intensive cholesterol-lowering for the reduction of major vascular events in a high-risk population, and of the effects of homocysteine-lowering with folic acid plus vitamin B12.
- No clear contraindication to study treatments
- Screening plasma total cholesterol <3.5 mmol/l in patient already on statin therapy, or <4.5 mmol/l in patient not on statin therapy
- Chronic liver disease
- Severe renal disease or evidence of renal impairment
- Inflammatory muscle disease
- Concurrent treatment with fibrates or high-dose niacin
- Concurrent treatment with cyclosporin (or condition likely to result in organ transplantation and the need for cyclosporin), nefazodone, methotrexate, systemic azole antifungal or systemic macrolide antibiotics
- Child bearing potential
- No other predominant medical problem (other than coronary heart disease [CHD]) which might limit compliance with 5 years of study treatment
United Kingdom, Oxon
CTSU, Richard Doll Building, University of Oxford, Oxford, Oxon, OX3 7LF, United Kingdom
Rory Collins, MB BS FRCP, Study Director, University of Oxford
Last Updated: August 4, 2005
Record first received: July 22, 2005
ClinicalTrials.gov Identifier: NCT00124072
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
ClinicalTrials.gov processed this record on 2005-08-23