Clopidogrel for Acute Ischaemia of Recent Onset

1. First ever presentation with acute ischemic stroke. Previous transient ischemic attacks (TIA's) are not excluding, regardless of their frequency or severity
2. Ictus to drug time does not to exceed 9 hours (allowing for at least 30 minutes to obtain imaging)
3. Patients with undetermined time of onset will be included only if they were last seen well within the same time window (9hrs). Onset of events in patients presented with stuttering stroke will be considered from the onset of the first clinical manifestation.
4. According to National Institute of Health Stroke Scale (NIHSS) on admission, patient will be recruited with NIHSS between 4 and 24 (both inclusive).

Exclusion Criteria:

1. Patients eligible for intravenous (recombinant tissue plasminogen activator) rTPA thrombolysis or thrombectomy.
2. If NIHSS on admission is 3 or less, 25 or more, or patients who are showing rapidly resolving symptoms prior to the results of imaging.
3. Clinical seizures at the onset of stroke.
4. Patients with known history or manifestations of any major organ failure.
5. Patients who have had acute myocardial infarction within 1 month; and/or with management interfering with the current study (e.g. warfarin).
6. Patients with active malignancies, and/or have been on chemo- or radiotherapy within the last year.
7. Patients with active peptic ulcer and/or (gastrointestinal tract) GIT surgery or bleeding within the last year.
8. Persistent uncontrolled vomiting during the first day of admission.
9. Patients with major surgery within the last 3 months.
10. Patients with history of uncontrolled bleeding site, within the prior year.
11. Patients with known allergy to study drugs.
12. Patients with known history of persistent or recurrent (central nervous system) CNS pathology (e.g. epilepsies, meningioma, multiple sclerosis).
13. Patients with past history of head trauma with residual neurological deficit
14. Patients who are on regular Clopidogrel during the week before admission.
15. Patient with raised prothrombin time (PT) on admission, either on anticoagulants (with raised INR>1.3, PT >18 second) or not (PT> 15 second), or on drugs that might increase possibility of peripheral bleeding (e.g. corticosteroids).
16. Patients who have an indication for full anti-coagulation during the first week of their hospital stay will be retrospectively excluded.

17. Patients receiving anti-coagulants in deep venous thrombosis (DVT) prophylaxis doses will NOT be excluded:

    • Enoxaparin 40mg/d (or equivalent).
    • Heparin with partial thromboplastin time (PTT) not exceeding 50 seconds.
    • Oral anticoagulation with INR \<1.5.
18. Pregnancy or breast feeding
19. Stroke due to venous thrombosis
20. Hemorrhagic stroke
21. Blood pressure \< 90/60 or > 185/110 mmHg, if not responding to intravenous antihypertensive therapy or requiring aggressive treatment to reduce it below this limit
22. Arterial puncture in a non-compressible site within the previous week
23. Strokes following cardiac arrest or profuse hypotension.
24. Blood glucose level \< 50 or > 400 mg/dl on admission
25. CBC with picture of severe anemia (Haematocrit \<0.25), thrombocytopenia (Platelets \< 100,000) or leucopenia (WBC \< 3,000).
26. Significant electrolyte imbalance that may account for the presenting manifestations
27. Contraindications to imaging

28. Urgent brain CT revealing any of the following:

    • Hemorrhage.
    • Major cerebral non-vascular pathology.
    • Suspected arterio-venous malformation (AVM).
    • Previous intracerebral hemorrhage or old infarctions larger than 1.5 cm.
    • Massive acute hypo density in the brain region corresponding to the current symptoms.