NCT00097669

Brief Summary

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
8,164

participants targeted

Target at P75+ for not_applicable stroke

Timeline
Completed

Started Nov 1998

Longer than P75 for not_applicable stroke

Geographic Reach
19 countries

110 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 1998

Completed
6.1 years until next milestone

First Submitted

Initial submission to the registry

November 24, 2004

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 25, 2004

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2009

Completed
11.3 years until next milestone

Results Posted

Study results publicly available

September 25, 2020

Completed
Last Updated

September 25, 2020

Status Verified

January 1, 2014

Enrollment Period

10.6 years

First QC Date

November 24, 2004

Results QC Date

January 20, 2014

Last Update Submit

September 7, 2020

Conditions

Keywords

VITATOPSstrokepreventionmultivitaminshomocysteine

Outcome Measures

Primary Outcomes (1)

  • 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).

Study Arms (2)

Active VITATOPS Tablet (folic acid 2mg, B6 25mg , B12 500ug)

ACTIVE COMPARATOR

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

Placebo Tablet

PLACEBO COMPARATOR

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

Interventions

multivitamin

Also known as: VITATOPS study tablet
Active VITATOPS Tablet (folic acid 2mg, B6 25mg , B12 500ug)
PlaceboOTHER
Placebo Tablet

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (111)

JFK Hospital / Seton Hall University

New York, New York, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, United States

Location

South Carolina VA Hospital

Columbia, South Carolina, United States

Location

University of South Carolina

Columbia, South Carolina, United States

Location

Central Coast Neuroscience Research

Gosford, Australia

Location

Bankstown Hospital

New South Wales, Australia

Location

John Hunter Hospital

New South Wales, Australia

Location

Liverpool Hospital

New South Wales, Australia

Location

Royal Perth Hospital

Perth, Australia

Location

Greenslopes Hospital

Queensland, Australia

Location

Nambour Hospital

Queensland, Australia

Location

Flinders & Griffiths

South Australia, Australia

Location

Royal Hobart Hospital

Tasmania, Australia

Location

Alfred Hospital

Victoria, Australia

Location

Beleura & Frankston Hospital

Victoria, Australia

Location

Box Hill Hospital

Victoria, Australia

Location

National Stroke Research Institute - Austin Health

Victoria, Australia

Location

Fremantle Hospital

Western Australia, Australia

Location

Joondalup Hospital

Western Australia, Australia

Location

Sir Charles Gairdner Hospital

Western Australia, Australia

Location

Karl-Franzens University Graz

Graz, Austria

Location

Algemeen Ziekenhuis Sint-Jan Autonome Verzorgingsinstelling

Bruges, Belgium

Location

Universidade Federal Fluminense & Universidade Federal do Rio de Janeiro

Rio de Janeiro, Brazil

Location

Sarajishvili Institute of Neurology and Neurosurgery

Tbilisi, Georgia

Location

Queen Mary Hospital

Pokfulam, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Rajah Muthaiah Medical College

Annāmalainagar, India

Location

St John's Medical College Hospital

Bangalore, India

Location

SP Medical College

Bikaner, India

Location

Baby Memorial Hospital

Calicut, India

Location

KS Hospital

Chennai, India

Location

Care Hopstial

Hyderabad, India

Location

Mahaveer Hospital & Research Centre

Hyderabad, India

Location

Mediciti Hospital

Hyderabad, India

Location

MGM Medical College & MY Hospital

Indore, India

Location

Monilek Hospital

Jaipur, India

Location

Amrita Institute of Medical Science

Kochi, India

Location

Centauri, The Albert Road Clinic

Kolkata, India

Location

CSMMU

Lucknow, India

Location

Christian Medical College & Hospital

Ludhiana, India

Location

G.B. Pant Hospital

New Delhi, India

Location

Sir Ganga Ram Hospital

New Delhi, India

Location

Sadhbavana Medical & Heart Institute

Patiaala, India

Location

Railway Hospital

Perambūr, India

Location

Poona Hospital

Pune, India

Location

Ruby Hall Clinic

Pune, India

Location

Neurocenter

Trichy, India

Location

Care Hospital

Visakhapatnam, India

Location

Mahatma Gandhi Institute

Wardha, India

Location

Spedali Civili Di Brescia

Brescia, Italy

Location

Ospedale di Circolo de Busto Arsizio

Busto Arsizio, Italy

Location

Ospedale di Macerata

Macerata, Italy

Location

IRCCS Fondazione Istituto Neurologico C Mondino

Pavia, Italy

Location

Perugia Stroke Service & Citta Della Peive

Perugia, Italy

Location

University of Perugia

Perugia, Italy

Location

Ospedale R Guzzardi

Vittoria, Italy

Location

Hospital Universiti Sains Malaysia

Kelantan, Malaysia

Location

University of Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

City Emergency Hospital

Chishinau, Moldova

Location

Slotervaartziekenhuis

Amsterdam, Netherlands

Location

Oosterscheldeziekenhuis

Goes, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Auckland Hospital

Auckland, New Zealand

Location

Hawkes Bay Hospital

Hastings, New Zealand

Location

Palmerston North Hospital

Palmerston North, New Zealand

Location

North Shore Hospital

Takapuna, New Zealand

Location

Wellington Hospital

Wellington South, New Zealand

Location

KRL University

Islamabad, Pakistan

Location

Pakistan Institute of Medical Sciences

Islamabad, Pakistan

Location

DUHS - Civil Hospital

Karachi, Pakistan

Location

DUHS - Jinnah Hospital

Karachi, Pakistan

Location

POF Hospital Wah Cantt.

Wah Cantt, Pakistan

Location

Cagayan de Oro Medical Center

Cebu City, Philippines

Location

Cebu Doctor's Hospital

Cebu City, Philippines

Location

Cebu Velez General Hospital/ Visayas Comm. Medical Center

Cebu City, Philippines

Location

Chong Hua Hospital

Cebu City, Philippines

Location

Vicente Sotto Memorial Hospital

Cebu City, Philippines

Location

Cagayan Valley Medical Center

East Santiago City, Philippines

Location

Jose R Reyes Memorial Medical Centre

Manila, Philippines

Location

University Santo Tomas Hospital

Manila, Philippines

Location

Hospital Visconde de Salreu

Estarreja, Portugal

Location

Hospital de Santa Maria

Lisbon, Portugal

Location

Hospital Distrital de Oliverira de Azemeis

Oliveira de Azeméis, Portugal

Location

Hospital Geral de Santo Antonio

Porto, Portugal

Location

University of Novi Sad - Neurology & Neurosurgery

Novisad, Serbia

Location

Singapore General Hospital

Singapore, Singapore

Location

National Hospital of Sri Lanka

Colombo, Sri Lanka

Location

University of Kelaniya

Ragama, Sri Lanka

Location

University Hospital of North Staffordshire

Stoke-on-Trent, Shaffordshire, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Redbridge Health Care

Barking, United Kingdom

Location

Barnsley District Hospital

Barnsley, United Kingdom

Location

The Royal Victoria Hospital

Belfast, United Kingdom

Location

Bronglais General Hospital

Ceredigion, United Kingdom

Location

Western General Hospital, Edinburgh

Edinburgh, United Kingdom

Location

Royal Devon & Exeter Hospital

Exeter, United Kingdom

Location

Western Infirmary

Glasgow, United Kingdom

Location

St Luke's Hospital

Huddersfield, United Kingdom

Location

William Harvey Hospital

Kent, United Kingdom

Location

University Hospital Aintree

Liverpool, United Kingdom

Location

Altnagelvin Hospital

Londonderry, United Kingdom

Location

Luton and Dunstable Hospital

Luton, United Kingdom

Location

Royal Victoria Infirmary, Newcastle

Newcastle, United Kingdom

Location

North Tyneside District General Hospital

North Shields, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

St Mary's Paddington Hospital

Paddington, United Kingdom

Location

Rotherham General Hospital

Rotherham, United Kingdom

Location

Stirling Royal Infirmary

Stirling, United Kingdom

Location

Stepping Hill Hospital

Stockport, United Kingdom

Location

Musgrove Park Hosptial

Taunton, United Kingdom

Location

Torbay Hospital

Torquay, United Kingdom

Location

Related Publications (8)

  • Gommans J, Yi Q, Eikelboom JW, Hankey GJ, Chen C, Rodgers H; VITATOPS trial study group. The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial. BMC Geriatr. 2013 Sep 3;13:88. doi: 10.1186/1471-2318-13-88.

  • Hankey GJ, Ford AH, Yi Q, Eikelboom JW, Lees KR, Chen C, Xavier D, Navarro JC, Ranawaka UK, Uddin W, Ricci S, Gommans J, Schmidt R, Almeida OP, van Bockxmeer FM; VITATOPS Trial Study Group. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke. 2013 Aug;44(8):2232-9. doi: 10.1161/STROKEAHA.113.001886. Epub 2013 Jun 13.

  • Cavalieri M, Schmidt R, Chen C, Mok V, de Freitas GR, Song S, Yi Q, Ropele S, Grazer A, Homayoon N, Enzinger C, Loh K, Wong KS, Wong A, Xiong Y, Chang HM, Wong MC, Fazekas F, Eikelboom JW, Hankey GJ; VITATOPS Trial Study Group. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy. Stroke. 2012 Dec;43(12):3266-70. doi: 10.1161/STROKEAHA.112.665703. Epub 2012 Oct 23.

  • Hankey GJ, Eikelboom JW, Yi Q, Lees KR, Chen C, Xavier D, Navarro JC, Ranawaka UK, Uddin W, Ricci S, Gommans J, Schmidt R; VITATOPS trial study group. Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial. Lancet Neurol. 2012 Jun;11(6):512-20. doi: 10.1016/S1474-4422(12)70091-1. Epub 2012 May 2.

  • Hankey GJ, Eikelboom JW, Yi Q, Lees KR, Chen C, Xavier D, Navarro JC, Ranawaka UK, Uddin W, Ricci S, Gommans J, Schmidt R; VITAmins TO Prevent Stroke (VITATOPS) Trial Study Group. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: results of a randomized placebo-controlled trial. Stroke. 2012 Jun;43(6):1572-7. doi: 10.1161/STROKEAHA.111.641613. Epub 2012 Apr 3.

  • Almeida OP, Marsh K, Alfonso H, Flicker L, Davis TM, Hankey GJ. B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol. 2010 Oct;68(4):503-10. doi: 10.1002/ana.22189.

  • VITATOPS Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 2010 Sep;9(9):855-65. doi: 10.1016/S1474-4422(10)70187-3. Epub 2010 Aug 3.

  • VITATOPS Trial Study Group; Hankey GJ, Algra A, Chen C, Wong MC, Cheung R, Wong L, Divjak I, Ferro J, de Freitas G, Gommans J, Groppa S, Hill M, Spence D, Lees K, Lisheng L, Navarro J, Ranawaka U, Ricci S, Schmidt R, Slivka A, Tan K, Tsiskaridze A, Uddin W, Vanhooren G, Xavier D, Armitage J, Hobbs M, Le M, Sudlow C, Wheatley K, Yi Q, Bulder M, Eikelboom JW, Hankey GJ, Ho WK, Jamrozik K, Klijn K, Koedam E, Langton P, Nijboer E, Tuch P, Pizzi J, Tang M, Antenucci M, Chew Y, Chinnery D, Cockayne C, Loh K, McMullin L, Smith F, Schmidt R, Chen C, Wong MC, de Freitas G, Hankey GJ, Loh K, Song S. VITATOPS, the VITAmins TO prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444). Int J Stroke. 2007 May;2(2):144-50. doi: 10.1111/j.1747-4949.2007.00111.x.

Related Links

MeSH Terms

Conditions

StrokeIschemic Attack, Transient

Interventions

Folic AcidVitamin B 12

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesBrain Ischemia

Intervention Hierarchy (Ancestors)

PterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCorrinoidsTetrapyrrolesPyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds, 4 or More RingsMacrocyclic CompoundsPolycyclic Compounds

Results Point of Contact

Title
Clinical Trial Coordinator
Organization
VITATOPS

Study Officials

  • Graeme Hankey, MBBS/MD

    Royal Perth Hospital / University of Western Australia

    PRINCIPAL INVESTIGATOR
  • Ross Baker, MBBS/BMedSc

    Royal Perth Hospital

    STUDY DIRECTOR
  • John Eikelboom, MBBS/FRACP

    Royal Perth Hospital

    STUDY DIRECTOR
  • Konrad Jamrozik, MBBS

    The University of Queensland

    STUDY DIRECTOR
  • Frank van Bockxmeer, BSc/PhD

    Royal Perth Hospital

    STUDY DIRECTOR
  • Siobhan Hickling, BSc/MPH

    The University of Western Australia

    STUDY DIRECTOR
  • Anna Gelavis, BPharm

    Royal Perth Hospital

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 24, 2004

First Posted

November 25, 2004

Study Start

November 1, 1998

Primary Completion

June 1, 2009

Study Completion

June 1, 2009

Last Updated

September 25, 2020

Results First Posted

September 25, 2020

Record last verified: 2014-01

Locations