VITATOPS: A Study of VITAmins TO Prevent Stroke

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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VITATOPS - A Study of VITAmins TO Prevent Stroke

Conditions
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Stroke, Transient Ischemic Attack

Intervention / Treatment
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* Drug: Active VITATOPS Tablet (folic acid 2mg, B6 25mg , B12 500ug) or placebo
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting within seven months of stroke (ischemic or hemorrhagic) or TIA Agree to take study medication Be geographically accessible for follow-up Provide written informed consent Exclusion Criteria: Taking folic acid or B6 on medical advice Use of vitamin supplements containing folate, B6 or B12 (unless patient agrees to take study medication instead of the vitamin supplements which they usually take) Taking Methotrexate for any reason Pregnancy or women of child-bearing potential who are at risk of pregnancy Limited life expectancy
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active VITATOPS Tablet (folic acid 2mg, B6 25mg , B12 500ug)<br>Active Treatment Arm: VITATOPS study tablet (folate 2 mg, B6 25 mg, B12 500 ug). Taken daily for the duration of the study. | Drug: Active VITATOPS Tablet (folic acid 2mg, B6 25mg , B12 500ug) or placebo<br>* multivitamin<br>* Other names: VITATOPS study tablet;|
| Placebo Comparator: Placebo Tablet<br>Placebo Treatment Arm: The placebo tablet will have the same appearance, taste and texture as the vitamin preparation and contains excipients, coating and coating aids. | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-fatal Stroke, Non-fatal Myocardial Infarction or Death Due to Vascular Causes |  | The primary outcome was measured over a median follow-up period of 3.4 years (interquartile range IQR 1.0-5.5 years). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, VITATOPS, prevention, multivitamins, homocysteine