The VITATOPS study is a multi-center, randomized, double blind, placebo-controlled secondary stroke prevention trial to determine whether the addition of vitamin supplements (B12 500 ug, B6 25 mg, Folate 2 mg) to best medical/surgical management (including modification of risk factors) will reduce the combined incidence of recurrent vascular events (stroke, myocardial infarction) and vascular death in patients with recent stroke or transient ischemic attack (TIA). All patients presenting to one of the participating neurologists or general physicians within seven months of stroke (ischemic or hemorrhagic) or TIA (eye or brain) are eligible for this trial. Eligible patients will be randomized in a double-blind fashion to receive multi-vitamins or placebo, 1 tablet daily. The primary outcome event is the composite event "stroke, myocardial infarction, or death from any vascular cause", whichever occurs first. Our target is to recruit a total of 8,000 patients over the next two years with a median follow-up of 2.5 years. Recruitment to the trial began in November 1998 and is planned to continue until December 2005. We aim to complete final follow-up by the end of 2006. However, the Steering Committee will be flexible in dictating the need for ongoing recruitment and continuing follow-up, depending on the overall rate of the primary outcome event in the entire cohort at each interim analysis.
Background: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischemic stroke, dementia and depression. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B12 and vitamin B6, it is not known whether lowering tHcy, by means of multivitamin therapy, can prevent stroke and other major atherothromboembolic vascular events, dementia and depression.
Purpose: To determine whether vitamin supplements (folic acid 2 mg, B6 25 mg, B12 500 ug) reduce the risk of stroke, other serious vascular events, dementia and depression in patients with recent stroke or transient ischemic attacks of the brain or eye (TIA).
Methods: An international, multi-center, randomized, double-blind, placebo-controlled clinical trial.
Subjects: Patients with stroke or TIA in the previous 7 months.
Primary outcome measure: Non-fatal stroke, non-fatal myocardial infarction, or death due to vascular causes.
Secondary outcome measures: TIA, Revascularisation procedures, Dementia, Depression.
Sample size calculation: To reliably identify a 15% reduction in relative risk of the primary outcome event from 8% to 6.8% per year with an alpha of 0.05 and power of 80%, 8,000 patients need to be randomized and followed-up for an average of two years.
Current progress: As of November, 2004, more than 4,400 patients have been randomized in 73 centers in 19 countries in five continents: Australia, Austria, Belgium, Brazil, Hong Kong, Italy, Malaysia, Moldova, Netherlands, New Zealand, Pakistan, Philippines, Portugal, Republic of Georgia, Serbia & Monte Negro, Singapore, Sri Lanka, United Kingdom, and United States.
VITATOPS aims to recruit and follow up 8,000 patients between 2000 and 2006, and provide a reliable estimate of the safety and effectiveness of dietary supplementation with folic acid, vitamin B12, and vitamin B6 in reducing recurrent serious vascular events, dementia and depression among a wide range of patients with stroke and TIA.
- Vitamins Drug
Intervention Desc: Attempt to lower homocysteine by vitamin therapy (folate, B6, B12).
- Folic Acid (Folate, Folacin,)Drug
Intervention Desc: 2 mg
- Vitamin B6 Drug
Intervention Desc: 25mg
- Vitamin B12 Drug
Intervention Desc: 500ug
- Allocation: Randomized
- Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
- Purpose: Prevention
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
Patients are randomized in double-blind manner to receive either vitamin supplements [B(12) 500 ug; B(6) 25 mg; folate 2 mg] or a placebo, once daily. They are then to receive follow-up evaluations at 3 months, 6 months, and every 6 months thereafter until the 60-month follow-up period has been completed.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Non-fatal stroke, non-fatal myocardial infarction, or mortality due to vascular causes.|
|Secondary||TIA, revascularisation procedures, dementia, and depression.|
|Primary||Non-fatal stroke||trial end||Yes|
|Primary||Non-fatal myocardial infarction||trial end||Yes|
|Primary||Death due to vascular causes||trial end||Yes|
|Secondary||Revascularization procedures||trial end||Yes|