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*** APRIL UPDATE ***

APRIL 2006

Page

VITATOPS Update 1

Welcomes & Farewells 2

Misdiagnoses of Stroke/TIA 2

Extension of Trial/Follow-up 3

15th ESC & Investigator Meet- 3

Book Prize 3

Interim Analysis Update 3

Website Update 4

Collection of Vitamin B12 4

Depression & Dementia 4

Date Reporting 5

New Fax for Pharmacy 5

Medical University of Graz 5

Trial Office Contact Details 5

Active Sites 6-10

Prospective Sites 11

Drug Resupply Form 12

CONTENTS Welcome to the FIRST edition of the VITATOPS newsletter for 2006. Since July 2005 new sites in India and the UK have joined the study resulting in a significant increase in monthly recruitment totals. We welcome the following sites in India: Amrita Institute of Medical Science, Cochin; Poona Hospital, Pune and Ruby Hall Clinic. Number of Active Sites Participating: 94 Number of Countries Participating: 20 Number of Continents Participating: 5 Total Recruitment in NOV 2005: 98 Total Recruitment in DEC 2005: 108 Total Recruitment in JAN 2006: 124 Total Recruitment in FEB 2006: 94 Total Recruitment in MAR 2006: 64

Total Recruitment (31st March 2006): 5,728 Special CONGRATULATIONS to the top 3 re-cruiting sites in March; • SP Medical College, Bikaner: 10 patients • Singapore General Hospital: 6 patients • Care Hospital, Hyderabad: 6 patients

VITATOPS NEWSLETTER

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WELCOMES We welcome the following collaborators to the study and hope they enjoy participating on VITATOPS; Ana Dias – Hospital Do Visconde de Salreu Tessa Hammond – William Harvey Hospital Niels Kamerling – Algemeen Ziekenhuis Sint-Jan Autonome Versorginginstelling John Jones – University Hospital Aintree Nicola Sprigg – Nottingham City Hospital Venugopal Thattolicanhiratan – St Luke’s Hospital Daniel Vallini – South Carolina VA Hospital Martine Wilkinson – St Luke’s Hospital

FAREWELLS We farewell and thank the following collaborators for their contribution to the VITA-TOPS study and wish them all the best in the future; Katie Burlace – William Harvey Hospital Kevin Channell – University Hospital Aintree Eileen Conkie – Western Infirmary Shiraz Haider – St Luke’s Hospital Sabine Schindler – Medical University of Graz Mark Willmont – Nottingham City Hospital Nelson Wong – Singapore General Hospital

TRIAL OFFICE STAFF UPDATE We would like to thank Swee-Chin Bono for her collaboration on the VITATOPS study. We congratulate Swee-Chin on her new appointment as a full-time Pharmacy Assistant at the Royal Perth Hopsital Pharmacy Department.. Bianca Swarts is the new Phar-macy Technician for the VITATOPS Trial. Bianca can be contacted via e-mail on:

Bianca.Swarts@health.wa.gov.au

WELCOMES & FAREWELLS

MISDIAGNOSES OF STROKE/TIA

At a recent VITATOPS Steering Committee meeting the follow-up of patients recruited to the study with stroke/TIA, and who are later found to have been misdiagnosed, was dis-cussed. It was decided that these patients are no longer required to be followed-up.

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EXTENSION OF TRIAL & FOLLOW-UP BEYOND 5 YRS

There are now over 5,700 patients ran-domised to the trial. As we are still aim-ing to recruit 8,000 patients, the Steering Committee has recommended for ran-domisation to continue until at least mid 2007 and for follow up to continue until at least mid 2008. As each local Ethics Committee (EC) requirements differ the Trial Office recommends for collaborating sites to consult with their ECs (and Phar-macy Department if required) regarding extension for randomisation and follow-up beyond 5yrs. If patients agree to continue follow-up be-yond 5 yrs and new follow-up forms are required please contact the Trial Office. These forms can also be downloaded from the VITATOPS website.

INTERIM ANALYSIS UPDATE

An interim analysis was recently con-ducted in December 2005. At this time there were approximately 10,000 patient years of follow-up. The Data Safety Monitoring Committee concluded re-cruitment and follow-up SHOULD con-tinue.

BOOK PRIZE

Collaborating sites will have the opportunity to win Graeme Hankey’s recently published book “Stroke Treatment and Prevention: An Evidence-Based Approach”. Sites can win this prize in one of two ways; A book will be awarded to the site that ran-domises the 6,000th patient to the VITA-TOPS study. There are just over 270 pa-tients that remain to be recruited before this milestone is reached. Another prize will go to a site that completes and returns all data clarifications and out-standing follow-ups, as recently sent by Data Manager Corrie Cockayne. Eligible sites will be entered into a draw and the winning site will be notified via e-mail.

15th EUROPEAN STROKE CONFERENCE (ESC), BRUSSELS 16-19 MAY 2006

A meeting of VITATOPS Study Investiga-tors has been planned for the 15th ESC. The meeting will be held in conjunction with the CLOTS and ENOS trials. Please see below for meeting details; Date: Thursday, 18th May, 2006 Time: 12.30-14.00 Venue: Room 1125, Congress Building Dr Gabriel de Freitas (National Coordina-tor, Brazil) will be presenting this meet-ing on behalf of Graeme Hankey. Could you please notify the Trial Office if you and your colleagues will be able to attend the meeting. Furthermore, if you would like to include any items to the meeting agenda or request data for analysis please notify the Trial Office. Further details will be confirmed in an e-mail to collaborators shortly.

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WEBSITE UPDATE

You will now be prompted to enter your name when randomising patients via the VI-TATOPS on-line randomisation service. The website has also been modified to ensure that only patients who have suffered their randomising stroke/TIA within 7 months of recruitment to the study are successfully al-located a VITATOPS study number. If the patient had their randomising stroke more than 7 months prior to recruitment an error message will be displayed notifying you that the exclusion criteria has not been met.

COLLECTION OF VITAMIN B12 AT ENROLMENT

At a recent VITATOPS Steering Com-mittee meeting the collection of vitamin B12 at time of enrolment was discussed. The Steering Committee encourages sites to collect and record vitamin B12 levels at enrolment if available as part of routine testing. A field to report the patients B12 level is now included on the baseline case report forms. Modi-fied baseline forms are available via the VITATOPS website. If a patient’s vita-min B12 level at enrolment can be re-ported retrospectively please forward these results to the Trial Office.

DEPRESSION & DEMENTIA

A decision has been made by the Steering Committee to record depression and de-mentia as secondary outcome events on the blue major event (ME) forms. The ME forms have been modified to include these events as secondary outcomes. New ver-sions of the ME forms are available via the VITATOPS website. If you require hard copies to be posted to your site please contact the Trial Office.

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THE NEW FAX NUMBER TO

REQUEST TABLET STOCK IS

+61 8 9224 3696.

If tablet resupply is required

please provide at least 2

weeks notice to the VITATOPS

Pharmacy Dept to allow for

your request to be organised

and dispatched.

Please note, the former

site Karl-Franzens

University Graz is now

named MEDICAL

UNIVERSITY OF GRAZ.

DATE REPORTING

When reporting dates of birth or dates of events please adhere to the following guide-lines; 1. When the year is known but the day/ month is unknown please report 30/06/ year. 2. When the year and month is known but the day is unknown please report 15/month/year. 3. When the day/month/year is unknown please ask the patient to estimate the year by associating the date to an event in their life, eg. historical event, starting school).

TRIAL OFFICE CONTACT DETAILS

VITATOPS TRIAL OFFICE STROKE UNIT RESEARCH ROYAL PERTH HOSPITAL PO BOX X2213, PERTH WESTERN AUSTRALIA 6847

Phone: +61 8 9224 7004 (Julia Pizzi) Phone: +61 8 9224 3336 (Michelle Tang) Phone: +61 8 9224 8497 Fax: +61 8 9224 8424 Email: VITATOPS@health.wa.gov.au

PAGE 6 ACTIVE RECRUITMENT (CURRENT TO 31 March, 2006)

Site Principal Investigator Research Coordinator Total AUSTRALIA

Alfred Hospital, VIC Judy Frayne Joanne Ferguson 42 Bankstown, NSW Jim Kokkinos Cathy Smith 36 Beleura & Frankston, VIC Prakash Nayagam Penny Clayton 25 Box Hill Hospital, VIC Chris Bladin Kelly Coughlan 40 Central Coast, Gosford, NSW Dennis Crimmins Michelle Rose

Alison Slattery 102

Flinders & Griffith, SA David Schultz Sara Laubscher 53 Fremantle, WA Tim Davies Valentina Rakic 59 Greenslopes, QLD Carolyn de Wytt Patricia Wall 12 John Hunter, NSW Chris Levi

Mark Parsons Elizabeth Pepper

Michelle Russell 26

Joondalup, WA Jake Harper Pam Rees Denise Warden

29

Liverpool, NSW Alan McDougall Lorraine Ryan 4 Nambour, QLD Rohan Grimley 2 Royal Hobart Hospital, TAS David Dunbabin Julie Sansom 30 Royal Perth Hospital, WA Graeme Hankey Katherine Loh 469 Sir Charles Gairdner, WA Keith Grainger 16

AUSTRIA

**Medical University of Graz Reinhold Schmidt Franz Fazekas Anita Lechner Barbara Ebenbauer Silvia Legat-Wallner Gerald Pichler Birgit Reinhart Thomas Seifert Mirja Waller Sabine Weiss

173

BELGIUM

**AZ Sint-Jan AV Geert Vanhooren Niels Kamerling Valérie Schotte

52

BRAZIL **Universidade Federal Fluminense & Universidade Federal do Rio de Ja-neiro

Gabriel de Freitas Charles André

Silvio EG Gomes Lidia Conforto Miguel Picanco Simone do Valle

71

HONG KONG

**Prince of Wales Hospital Lawrence Wong Adrian Wong Roxanna Liu

83

**Queen Mary Hospital Raymond Cheung Liza Hui 18

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ACTIVE RECRUITMENT (CURRENT TO 31 March, 2006)

Site Principal Investigator Research Coordinator Total INDIA

Amrita Institute of Medical Sciences Suresh Kumar Vinayan K.P

9

Baby Memorial Hospital, Calicut Abdul Salam Ummer Karadan

Jayanth K. Savanth Laila Achambat Reena Mathew

59

Care Hospital, Hyderabad JMK Murthy 51 Care Hospital, Visakhapatnam Kishore Babu 18 Christian Medical College, Ludhiana Yashpal Singh

T.M. Jaison Jeyaraj D Pandian

42

G.B. Pant Hospital, New Delhi M.M. Mehndiratta S.M. Raheja

Chetan Ray 10

Mahavir Hospital & Research Centre, Hy-derabad

Sindhu Joshi 13

Mediciti Hospital, Hyderabad Umesh Tukaram 24 MGM Medical College & MY Hospital, In-fore

Anil Bharani 20

Monilek Hospital & Research Centre, Jaipur

Rajeev Gupta R R Agarwal

Harish Chandra 16

Neuro Centre, Trichy A Sundararajan 39 Poona Hospital, Pune Sudhir Kothari 20 Railway Hospital, Perambur, Chennai A Kalanidhi 7

Rajah Muthaiah Medical College, An-namalainagar

N. Chidambaram S.Balasubramanian

R.Umarani V.Anandi

39

Ruby Hall Clinic, Pune R.S. Wadia S. Bandhishti

5

SP Medical College, Bikaner DK Kochar 61

St John's Medical College Hospital A.K. Roy 24 ITALY

Citta della Pieve Stefano Ricci Maria Grazia Celani Tatiana Mazzoli Enrico Righetti Luciana Favorito

23

IRCCS C. Mondino Giuseppe Micieli Anna Cavallini Guido Giardini Simona Marcheselli Elena Zambrelli

4

Ospedale di Circolo, Busto Arsizio Severino Caprioli Michela Provisione Danilo Zanotta

5

Ospedale di Macerata Luigino De Dominicis Giorgio Giuliani

Roberto Caporalini Marilena Giovagnetti Eugenio Pucci Susanna Paoletti

18

**Perugia Stroke Service As for della Pieve As for della Pieve 67

PAGE 8 ACTIVE RECRUITMENT (CURRENT TO 31 March, 2006)

Site Principal Investigator Research Coordinator Total ITALY continued

Spedali Civili de Brescia Angelo Costa Mauro Magoni

Federica Casoni Raffaella Spezi Veronica Vergani Elisabetta Venturelli Rachele Tortorella

9

Uni of Perugia – Dept of Internal Medicine (Internal & CV Med)

Paolo Gresele

Francesco Guercini Ugo Paliani

20

MALAYSIA Hospital Universiti Sains Malaysia Jafri Malin Abdullah Saufi Awang

Zamzuri Idris Abdul Rahman Izani Ghani Sani Sayuti

68

**University of Malaya Medical Kay-Sin Tan Chong-Tin Tan

13

MOLDOVA City Emergency Hospital Stanislav Groppa Eremei Zota

Viorel Grigor Diana Manea

38

NETHERLANDS Oosterscheldeziekenhuis Rico Sips A.M.Boon

J.C. Doelman F. Visscher

37

Slotervaartziekenhuis Jaap van der Sande W Boogerd HL Hamburger VIH Kwa

12

University Medical Center, Utrecht J van Gijn Ale Algra

Patricia Halkes Moniek Boekweit

42

NEW ZEALAND Auckland, NZ Neil Anderson

Alison Charleston David Spriggs

Patricia Bennett 62

**Hawke’s Bay, NZ John Gommans Marie Pickup Diana Schmid

101

North Shore, NZ Joe Singh Sue Austin 12 Palmerston North, NZ John Bourke 6 Wellington Hospital Harry McNaughton 3

PAKISTAN POF Hospital, Wah Cantt. Wasim Uddin Muhammad Asim Anwar

Hassan Murtaza 140

PHILIPPINES Cagayan de Oro Med. Center Arturo Surdilla Lorena Absin 32 Cagayan Valley Med Center Generaldo Maylem Rex Cubero 1 Cebu Doctor’s Hospital Maria Teresa Canete 84 Cebu Velez General Hospital / Visayas Comm Med Center

Maria Teresa Canete 124

Chong Hua Hospital Maria Teresa Canete 133 **Jose R. Reyes Mem MC Jose Navarro Ciela Balagtas

Macrine Grace Amato 411

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ACTIVE RECRUITMENT (CURRENT TO 31 March, 2006)

Site Principal Investigator Research Coordinator Total

PHILIPPINES Continued

University of Santo Tomas Hospital Johnny Lokin Chinkee Araullo

Leticai Araullo Maricar Yumul

12

Vicente Sotto Memorial Medical Center Maria Teresa Canete 55

PORTUGAL **Hospital de Santa Maria Josè M. Ferro Marisa Costa 21 Hospital Distrital Oliveira de Azeméis Miguel Veloso Elizabeth Marques 61 Hospital Do Visconde de Salreu Ana Paula Sousa Ana Dias 13 Hospital Geral de Santo Antonio Manuel Correia Gabriela Lopes 35

REPUBLIC OF GEORGIA **Sarajishvili Institute of Neurology Alexander Tsiskaridze Tamara Vashadze 118

SERBIA & MONTE NEGRO **University of Novi Sad - Neurology Ivana Divjak Ksenija Bozic

Mirjana Bukinac Vera Diklic Slobadan Gvozdenovic Aleksandar Jovanovic Mirjana Joviecevic Marija Zarkov Milorad Zikic

61

University of Novi Sad – Neurosurgery Ivana Divjak Ljubomir Popovic Tomislav Cigic Djordje Jajic Bozidar Kaurinovic Zeljko Kojadinovic Vladimir Papic Petar Vulekovic

22

SINGAPORE

**Singapore General Christopher Chen Nelson Wong Siew Li Tan

737

SRI LANKA **National Hospital of Sri Lanka Udaya K. Ranawaka

Jagath Wijesekera Muditha Weerakkody 274

UNITED KINGDOM

Altnagelvin Hospital Mark McCarron Mary McNicholl 6

Barking Hospital, Redbridge, Essex, UK Kantha Niranjan 1

Barnsley District Hospital MK Albazzaz Bernadette Hardware 37

Bronglais General Hospital Philip Jones Sarah Roberts 37

PAGE 10 ACTIVE RECRUITMENT (CURRENT TO 31 March, 2006)

Site Principal Investigator Research Coordinator Total UNITED KINGDOM Continued

Luton & Dunstable Hosptial, UK Sekaran Lakshmanan Sakthivel Sethuraman 11 North Tyneside, UK Richard Curless Judy Murdy 152 Nottingham City Hospital, UK Philip Bath

Nikola Sprigg Ulrike Ferentzi Fiona Hammonds

30

Royal Victoria, Belfast, UK Michael Watt Annemarie Hunter 118 Royal Vic Infirmary, Newcastle Helen Rodgers Judy Murdy 92 St Luke’s Hospital Badr El din Ahmed Dafalla

P Rana Venugopal Thattolicanhiratan S Z Tun Dawn Connolly Samantha Wright

13

St Marys Paddington Jeremy Chataway Rahman Chowdhury 7 Stirling Royal Infirmary Alan McKenzie Fiona Dick 2 University Hospital Aintree Anil Sharma Elalaine Bacabac

John Jones Maria Koufali

15

Western General, Edinburgh, UK Martin Dennis Sharon Cameron Hayley Cuthbert Kareen Darley Dawn Lyle Barbara McLaren

131

**Western Infirmary, Glasgow Kennedy Lees Jesse Dawson Matthew Walters Lesley Campbell Yvonne Mcilvenna

299

William Harvey Hospital David Smithard Linda Cowie 44

USA Abington Memorial , USA Kevin R. Booth Michelle Young-Stevenson 4 JFK Hospital / Seton Hall University

Michael Moussouttas Anabel Doumad Susan Fowler Nikolaos Papamitsakis Jennifer Taylor

21

**Ohio State University, USA Andrew Slivka Peggy Notestine 15 South Carolina VA Hospital (recruitment potential reached)

Daniel Vallini 12

University of South Carolina (recruitment potential reached)

Te-Long Hwang Michelle Saverance 7

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PROSPECTIVE SITES

Country Centre Principal Investigator Current Status

Australia National Stroke Research Institute - Austin Health

Geoff Donnan Seeking ethics approval

India K.S. Hospital, Chennai R.S Muralidharan Ethics application approved King George’s Medical College, Lucknow

Maneesh Singh Atul Agarwal

Ethics application submitted

Krishna Institute of Medical Sciences, Hyderabad

Chandra Sekhar Reddy Seeking ethics approval

Mahatma Gandhi Institute of Medical Sciences (MGIMS), Wardha

S P Kalantri Ethics application approved

Sadbhavana Medical & Heart Institute, Patiala

Harminder Singh Ethics application approved

Sir Ganga Ram Hospital, New Delhi Anshu Rohatgi Ethics application submitted

Sri Ramachandra Hospital, Chennai CU Velumurugandran Ethics application approved

Pakistan Dow University of Health Sciences - Civil Hospital, Pakistan

Javed Ismail Ethics application approved

Dow University of Health Sciences - Jinnah Hospital, Pakistan

Javed Ismail Ethics application approved

Philippines West Visayas State University Medical Center, Iloilo City, Philippines

Ryndell G. Alava Seeking ethics approval

Sri Lanka CTU, University of Kelaniya, Sri Lanka Asita de Silva Udaya Ranawaka

Ethics application approved

Sultanate of Oman

Royal Hospital, Muscat George Paulose Shelley Pillai

Seeking ethics approval

Canada McMaster University Chidam Yegappan Seeking ethics approval Robarts Research Institute David Spence Ethics application approved

Saskatoon Christopher Voll Seeking ethics approval University of Calgary Michael Hill Ethics application approved

UK City General Hospital Christine Roffe Ethics application approved

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DRUG SUPPLY

VITATOPS STUDY

FAX TO: Naomi Lillywhite/Bianca Swarts Royal Perth Hospital Fax No: Australia 08 9224 3696

International +61 8 9224 3696 No cover sheet necessary Date: _________ Investigator: __________ Pharmacist: ______________ Delivery Address: __________________ __________________ __________________ __________________ Drug supplies required: _____________________ _____________________ Date required by: ____________