Study CL3-18886-012 Centre Feasibility questionnaire - Main study

We would greatly appreciate if you could return the completed questionnaire via E-Mail or Fax to PAREXEL International by no later than May 19th.

COUNTRY: DEPARTMENT: ADDRESS:

Mexico................................................... Neurology................................................ Costera M. Alemn 218, Centro Comercial Kennedy, Local 304 y 305, Fraccionamiento Magallanes. C.P. 39670....... Acapulco................................................. Neurology................................................ 0052 744 4858585..................................... ........................................................... enrique_garciac@hotmail.com ......................... 16/05/06................................................

INVESTIGATOR NAME: Dr. Garcia Cuevas Enrique.............................

CITY: SPECIALITY: PHONE: FAX: E-MAIL: DATE:

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Summary
S 18886 is a TP-receptor antagonist (i.e. specific antagonist of thromboxane A2 and prostaglandin endoperoxide) MAIN STUDY OBJECTIVE The primary objective is to compare the efficacy of S 18886 versus aspirin in reducing cerebral and cardiovascular events of atherothrombotic origin (primary efficacy end point: composite of cardiovascular death, or non fatal ischemic stroke, or non-fatal myocardial infarction) in patients with a history of ischemic stroke (IS) or transient ischemic attack (TIA). The secondary objectives are to assess the effect of S 18886 on the other efficacy endpoints and its safety. STUDY DESIGN Pivotal, phase III, international, multicentre, randomized, double-blind, two parallel groups, controlled versus aspirin study.

SELECTION / INCLUSION CRITERIA Women or men, age55 years,

Patient having suffered an ischemic stroke (IS) or an arterial retinal ischemic event (ARIE) (only if confirmed by an ophthalmologist), more than 48 hours and less than 3 months before having presented a transient ischemic attack (TIA) only if diagnosed by a neurologist or an anacrusis fugal within 8 days before randomization. All efforts should be made in order to include the patient as soon as possible within this time-window.

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 To meet the definition of IS or ARIE, the patient must satisfy the following criteria: Focal ischemic neurological deficit

Duration 24 hours

Or with CT scan/MRI evidence of associated corresponding brain infarction, regardless of the duration of symptoms

Or having presented a transient ischemic attack (TIA) only if diagnosed by a neurologist or an anacrusis fugal within 8 days before randomization; to meet the definition of TIA, patients must satisfy the following criteria: Focal ischemic neurological deficit Duration < 24 hours, in the absence of CT scan/MRI evidence of associated corresponding brain infarction.

Neurologically, clinically and haemodynamically stable at inclusion according to the investigator's opinion (neurological stability is a neurological state sufficiently stable to allow sure identification of a new stroke in the same territory). Result of a CT-scan or a MRI ruling-out intracranial haemorrhage or any nonischaemic neurological disease.

Giving informed consent before inclusion. NON-SELECTION/EXCLUSION CRITERIA (Main Criteria)

Modified Rankin scale > 4 (i.e. severe disability: patient bedridden, incontinent and requiring Constant nursing care and attention). Cognitive impairment interfering with the conduct of the study and the possibility to obtain patient's informed consent, Any known high risk source of cardioembolism, such as mechanical prosthetic valve, mitral stenosis with atrial fibrillation, atrial fibrillation, left atrial/atrial appendage thrombus, sick sinus syndrome, myocardial infarction within 3 months of inclusion, left ventricular thrombus, dilated cardiomyopathy, akinetic left ventricular segment, atrial myxoma, infective endocarditis. Acute stroke of other determined etiology (arteritis, dissection, prothrombotic state, drug abuse) Iatrogenic stroke, such as induced by vascular procedure endarterectomy, any angiography, endovascular interventions, CABG) (carotid

Carotid endarterectomy or stenting performed within 30 days prior to inclusion Carotid endarterectomy already planned in the next 6 months at the time of randomization
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I.
1)

Activity in your department

How many patients do you treat each year?
with ischaemic stroke with transient ischaemic attack 10 /year 150 /year

Among the ischaemic stroke patients, please, specify the percentage of patients

with:

- Large artery disease: - Small artery disease (lacunar): - Cardiogenic embolism: - Unknown origin: How

30 % 20 % 20 % 30 %

long after the stroke are these patients usually admitted to your department?
< 24 hours <1 a 3 days

2)

During the acute phase of ischaemic stroke, what are the usual treatments prescribed in your department? (please specify name, and duration)
Hiperventilation Manitol Aspirin or Clopidrogel

After the acute phase (secondary prevention), for 100 patients with ischaemic stroke of non cardio-embolic origin treated in your department, how many are treated with:
Number of patients Aspirin (specify the dosage mg/d) Clopidogrel Ticlopidine Dipyridamole-Aspirin Statin Other lipid lowering ACE inhibitor/ Angiotensin inhibitor Benzodiazepin Other, please specify: - - - |60%| |30%| || || |30%| |30%| |60-70%| || || || || Days started after the event 1........... days 1........... days . . days . . days 1........... days 1........... days 1........... days . . days . . days . . days . . days Duration days or months Mosnts
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3)

Is a CT-scan or a MRI systematically performed for the patients with stroke followed in your department? Yes x No
If yes, when do you perform it ? 1.......... days after the event Which other investigation(s) do you usually perform to explore these patients ? - A cervical doppler echotomography Yes x - Other, specify :.............................................Yes No No

Concerning CT-scan or MRI, which support can the radiology department of your hospital provide?
- X-ray negatives or paper format - Electronic file Yes x Yes No No

If electronic file, could you specify if it could be transferred into ?

DICOM JPEG PDF Other, specify

4)

On average, how long patients usually stay in these different departments?

Acute stroke unit Neurology department Other departments : ...... days 8 - 15..... days - .................... - ....................

days days

II. Your perspectives in this study

1) Are you willing to participate in this trial?
If no, please comment below : If yes, how many patients do you expect to enrol within the 2-year recruitment Yes x No Recruitment period March 2006-March 2008 and a maximum of 4-year follow up till March 2010

period (March 2006 March 2008)?

If no, specify :

200 patients Yes x No

After hospital discharge, are you able to follow your patients?

2)

What in the proposed study design could limit your recruitment (inclusion criteria, exclusion criteria, comparator)?
Exclusion criteria

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3)

Is there any competitive study during the planned recruitment period March 2006 March 2008? No

4)

In case of suspected post-stroke dementia, where is performed the cognitive impairment exploration?
- In your department - In another department Please, specify : Who is in charge of the psychometric evaluation? - Nurse - Neurologist - Psychologist - Other Please, specify : Is it possible to obtain an MRI evaluation within one month following a diagnosis of Yes Yes x Yes Yes No No No No Yes x Yes No No

post stroke dementia?

Yes

No x

III. Ancillary sub-studies

1) Vascular sub-study
Are you willing to participate in the Vascular sub-study? If yes, all your patients should be involved Yes If so, do you have easy access to IMT measurement ? - In your department - In a nearby vascular department Please, specify

No x

Yes Yes

No No

If you agree to participate, the specific vascular questionnaire has to be completed by the person in charge of IMT measurement

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2)

Biomarkers sub-study
Are you willing to participate in the Biomarkers sub-study? If yes, all your patients should be involved Yes

No x

3)

Pharmacokinetic sub-study
Are you willing to participate in the Pharmacokinetic sub-study? If yes, all your patients should be involved (i.e PK evaluation over 4-8 hours) Yes No

4)

Quality of Life sub-study

Are you willing to participate to the Quality Of Life sub-study? If yes, all your patients should be involved Yes x

No

5)

MRI sub-study
Are you willing to participate in the MRI sub-study? If yes, all your patients should be involved If so, do you have easy access to MRI equipment? - In your department - In a nearby MRI department Please, specify

Yes

No x

Yes Yes

No No

If you agree to participate, the specific MRI questionnaire has to be completed by the person in charge of the MRI

IV. Your experience in clinical trials

1) Have you previously participated in stroke trials?
Yes x No

If yes, in which trials were you involved and how many patients did you recruit? - Acute Ischemic Stroke Care in Hispanic Mestizos a Mexican Multicentric Ischemic Stroke Registry (44 patients) - -

2)

Are you familiar with ICH and GCP Guidelines?

Yes

No x

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3)

Is it possible for the monitor to have direct access to medical files of your patients? Yes No x

V. Logistics
1) For this study, will you have access to:
x a direct phone-line x a fax machine a 12-lead ECG a cooled centrifuge (2-8C) * an ultracentrifuge (10 000 g)* a 20C freezer with place available for the study samples a 80C freezer with place available for the study samples**

* Needed for pharmacokinetics and biomarkers** sub-studies

2) 3)

Have you already used an electronic Case Report Form (e-CRF)?

Yes

No x No

Do you have an internet access available for filling in the e-CRF? Yes x

Will there be a person of your department responsible for data entry in the e-CRF? Yes No x Please, specify the position of this person : Would it be also an internet access possible for the monitor for several hours together with the documents needed (patient medical file) during his/her visits? Yes x No

Be informed that you will have later to fill in a specific questionnaire to assess your Information Technology (IT) capabilities
4) Do you think that it will be possible to retrieve all documents to assess an endpoint if your patient is hospitalised somewhere else? (e.g: CT-scan or MRI for recurrent stroke,
cardiac enzymes and ECG for MI, hospital report..)

Yes x

No

5) 6)

Please, provide an e-mail address that could be used for this study:
enrique_garciac@hotmail.com

Please, provide contact address of the IT department of your hospital, if applicable:

Name of contact person : Phone number : + E-mail address:
Country

City

..... / . /

.............
Phone

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7)

Are you familiar with IVRS (automatic randomisation by phone)? Yes

Is vocal frequency available on your phone? Yes

No x No

8)

Have you already worked with a central laboratory for biological analysis?
Yes No x

9)

Are there any other departments to be contacted for the conduct of the study?
If YES, which one(s)? Local EC Administration Emergency Unit Rehabilitation Unit Pharmacist Radiology Biology laboratory 0thers, please specify : Yes x No

...................................................................................................... ...................................................................................................... x.............................................................................................................. x.............................................................................................................. x.............................................................................................................. x.............................................................................................................. x.............................................................................................................. Unit of Intensive Cares....................................................................

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