The second Meeting of Interregional Scientific and Technological Collaboration Palic, October 1314 2

1
The second Meeting of Interregional Scientific
and Technological Collaboration Palic, October
13-14 2006

• The VITATOPS
• (VITAmins TO Prevent Stroke) Trial multilateral
  collaboration
• Ivana Divjak on behalf of the VITATOPS Trial
  Study Group
• Medical Faculty Novi Sad, University of Novi Sad
  
• Principal investigator Clinical Professor Graeme
  J Hankey
• Stroke Unite-Research Office
• Royal Perth Hospital
• Western Australia

2

• Epidemiological studies suggest that raised
  plasma concentrations of total homocysteine
  (tHcy) may be a common, causal and treatable risk
  factor for atherothromboembolic ischaemic 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.

3

• VITATOPS study is an international multi-centre,
  randomised, double-blind, placebo controlled
  clinical trial designed primarily to examine the
  efficacy and safety of multivitamin (folate, B6,
  B12) therapy in the prevention of stroke,
  myocardial infarction, or death from any vascular
  cause. The trial is investigator-driven.

4

• Aim - to test the null hypothesis that
  homocysteine-lowering therapy with a multi
  vitamin tablet has not effect, compared with
  placebo, in preventing important vascular events
  among TIA and stroke patients.
• Methods - An international, multi-centre,
  randomised, double-blind, placebo-controlled
  clinical trial.
• Subjects - recent (within past 7 months) TIA
  or stroke
• Intervention - multivitamin tablet (folate 2 mg,
  vitamin B6 25 mg, vitamin B12 0.5mg)
• Follow-up - six monthly

5
VITATOPS Investigator Meeting15th European
Stroke Conference, Brussels

• AGENDA
• Welcome Introduction
• VITATOPS Trial Progress
• Preliminary Analyses
• Demographic and Follow-Up Data
• Future Issues
• Strategies to Increase Recruitment
• Completeness of Follow-ups
• Reporting Outcome Events
• Next International Steering Committee
  Teleconference
• Future Meetings
• Other Business

6
(No Transcript)
7
Total Patients Randomised as of 12th May
2006 5,808
8
Collaborating Centres
United Kingdom
Republic of Georgia
Sarajishvili Institute of Neurology Neurosurgery
United States
Europe
Prince of Wales Hospital Queen Mary Hospital
Pakistan
POF Hospital Wah Cantt.
Europe
Republic of Georgia - 1
United Kingdom - 16
India
United States - 5
Hong Kong
Pakistan - 1
Austria - 1 Belgium - 1 Italy - 7 Moldova -
1 Netherlands - 3 Portugal - 4 Serbia Monte
Negro - 2
Abington Memorial Hospital JFK Hospital/Seton
Hall University Ohio State University South
Carolina VA Hospital University of South
Carolina
Hong Kong - 2
India - 17
Sri Lanka
Malaysia
Philippines
Philippines - 7
National Hospital of Sri Lanka
Sri Lanka - 1
Malaysia -2
Singapore
Singapore -1
Singapore General Hospital
Brazil- 1
Hospital Universiti Sains University of Malaya
Medical Centre
Australia - 15
Royal Perth Hospital
New Zealand - 5
Australia
Brazil
Universidade Federal do Rio de Janeiro Universidad
e Federal Fluminense
Royal Perth Hospital
94 centres 20 countries 5
continents
http//www.graphicmaps.com
9
VITATOPS International Steering Committee

• Dr Christopher Chen (Singapore)
• Dr Raymond Cheung / Dr Lawrence Wong (Hong
  Kong)
• Dr Ivana Divjak (Yugoslavia)
• Professor José Ferro (Portugal)
• Dr Gabriel R. de Freitas (Brazil)
• Dr John Gommans (New Zealand)
• Professor Stanislav Groppa (Moldova)
• Professor Graeme Hankey (Australia)
• Assistant Professor Michael Hill (Canada)
• Professor Kennedy Lees (United Kingdom)
• Dr W Hugo G Lieuwens (The Netherlands)
• Professor Liu Lisheng (China)
• Dr Jose C. Navarro (Philippines)
• Dr Udaya Ranawaka (Sri Lanka)
• Dr Stefano Ricci (Italy)
• Associate Professor Reinhold Schmidt (Austria)
• Professor David J Spence (Canada)
• Dr Andrew Slivka (United States)
• Dr Kay-Sin Tan (Malaysia)

10
Recruitment by Country(as of 30th April 2006)
11
Preliminary Analyses

• Demographic Data
• Follow-up Data

12
Clinical syndromes
13
Risk factors
14
Risk factors
15
Risk factors
16
Person-Years of Follow-Up

• 12,143

17
Follow-Up
18
Delayed Follow-Up

• 1,384 patients

19
Delayed Follow-Up
Excluding patients who have died
20
Delayed Follow-Up
Excluding patients who have died and who have
asked for no continuation of follow-up
21
Discontinuation Rate

• 13.7

22
Discontinuation Rate
23
Outcome Events
24
Primary Outcome Events
25
Primary Outcome Events
26
VITAmins TO Prevent Stroke (VITATOPS)

• Primary outcome new Stroke, MI or vascular death
• 8 per year in control group
• 6.8 per year in treated group (15 RRR)
• sample size 8,000 (90 power)
• Secondary outcomes depression, dementia,
  revascularisation procedures, unstable angina

27
Homocysteine and risk of stroke and IHD The
Homocysteine Studies Collaboration. JAMA 2002
288 2015-2022.

• Systematic review, 1966-1999 of 30 studies
• 1113 stroke events 5073 IHD events
• 25 lower tHcy concn (3 micromol/l)
• 19 (5 to 31) lower risk of stroke
• 11 (4 to 17) lower risk of IHD
• Stronger assocns in retrospective studies of
  tHcy measured after onset of event, than
  prospective studies of people with no history of
  vascular disease when blood collected.

28
Prospective Centres

• Australia - 1 centre
• Canada - 4 centres
• India - 4 centres
• Italy - 1 centre
• Pakistan - 2 centres
• Philippines - 1 centre
• Sri Lanka - 1 centre
• UK - 4 centres

29
Acknowledgment

• National Health and Medical Research Council of
  Australia
• National Heart Foundation of Australia
• Health Department of Western Australia
• Blackmores Ltd
• Medical Research Council of UK

30
Completeness of Follow-Ups

• Outstanding / Delayed Follow-ups
• 2005 1,613 patients
• 2006 1,384 patients
• Reasons for Follow-up Delay
• not forwarding the forms.
• patient did not attend follow-ups, however site
  did not notify the Trial Office.

31
Completeness of Follow-Ups

• Reasons for Follow-up Delay
• not forwarding the forms
• patient did not attend follow-ups, however site
  did not notify the Trial Office
• ?????
• Solutions
• fax immediately after follow-up (within 5-7days)
• if follow-up was not completed - Did Not Attend
• withdrawn patients - site to inform Trial
  Coordinators and fax form stating for no further
  follow-up

32
Follow-Ups

• Discontinuation Rate
• 2003 8.5
• 2004 9.2
• 2005 11.7
• 2006 13.7

33
Completeness of Follow-Ups

• Outstanding Major Event Forms
• 355 outstanding major event forms
• ??? under-reporting of events
• Reasons for Delay
• ???
• Solutions
• fax MEFs immediately - site to inform Trial
  Office if awaiting further information for the
  event

34
Future Issues

• Strategies to Increase Recruitment
• Completeness of Follow-Ups
• Reporting of Outcome Events
• Next International Steering Committee
  Teleconference
• Future Meetings