Clopidogrel for Acute Ischaemia of Recent Onset

Study Overview
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Brief Summary
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Evaluate the role of loading Clopidogrel in acute ischemic stroke in improving neurological outcome of stroke in cases patients will be non-eligible for, or declined, treatment with or intravenous thrombolysis with rTPA, rTPA is not available or thrombectomy.

Official Title
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Clopidogrel Loading for Acute Ischaemia of Recent Onset (CAIRO)

Conditions
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Ischemic Cerebrovascular Accident

Intervention / Treatment
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* Drug: Clopidogrel
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First ever presentation with acute ischemic stroke. Previous transient ischemic attacks (TIA's) are not excluding, regardless of their frequency or severity Ictus to drug time does not to exceed 9 hours (allowing for at least 30 minutes to obtain imaging) 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. 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: Patients eligible for intravenous (recombinant tissue plasminogen activator) rTPA thrombolysis or thrombectomy. 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. Clinical seizures at the onset of stroke. Patients with known history or manifestations of any major organ failure. Patients who have had acute myocardial infarction within 1 month; and/or with management interfering with the current study (e.g. warfarin). Patients with active malignancies, and/or have been on chemo- or radiotherapy within the last year. Patients with active peptic ulcer and/or (gastrointestinal tract) GIT surgery or bleeding within the last year. Persistent uncontrolled vomiting during the first day of admission. Patients with major surgery within the last 3 months. Patients with history of uncontrolled bleeding site, within the prior year. Patients with known allergy to study drugs. Patients with known history of persistent or recurrent (central nervous system) CNS pathology (e.g. epilepsies, meningioma, multiple sclerosis). Patients with past history of head trauma with residual neurological deficit Patients who are on regular Clopidogrel during the week before admission. 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). Patients who have an indication for full anti-coagulation during the first week of their hospital stay will be retrospectively excluded. 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. Pregnancy or breast feeding Stroke due to venous thrombosis Hemorrhagic stroke 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 Arterial puncture in a non-compressible site within the previous week Strokes following cardiac arrest or profuse hypotension. Blood glucose level < 50 or > 400 mg/dl on admission CBC with picture of severe anemia (Haematocrit <0.25), thrombocytopenia (Platelets < 100,000) or leucopenia (WBC < 3,000). Significant electrolyte imbalance that may account for the presenting manifestations Contraindications to imaging 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 900 mg Clopidogrel<br>67 patients will receive 12 tablets clopidogrel ( each 75 mg) as total 900 mg each patient | Drug: Clopidogrel<br>* there is 2 groups one group will receive 900 mg Clopidogrel and the other will receive 600 mg Clopidogrel<br>* Other names: Srtoka;|
| Active Comparator: 600 mg Clopidogrel<br>67 patient will receive 8 tablets clopidogrel (each 75 mg) as total 600 mg each patient and 4 tablets placebo to receive 12 tablets as total | Drug: Clopidogrel<br>* there is 2 groups one group will receive 900 mg Clopidogrel and the other will receive 600 mg Clopidogrel<br>* Other names: Srtoka;|
| Placebo Comparator: 400 mg Aspirin<br>67 patients will receive 4 tablets Aspirin ( each 75 mg) as total 300 mg for each patient and 8 tablets placebo to receive 12 tablets as total | Drug: Aspirin<br>* there's another group will receive 400 mg Aspirin<br>* Other names: Aspocid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of NIH stroke scale score | Patients will be assessed for early neurologic improvement or deterioration using the change of NIH stroke scale score. Early neurological outcome | Baseline and up to 1 week | 
| Neurologic outcome | patients will be assessed for neurologic outcome using the Modified Ranking Scale at 3 months after onset | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding complications of loading clopidogrel | will follow cerebral bleeding complications using CT scan, and systemic bleeding complications (GI bleeding, hematuria, etc.) that may occur following the loading dose | 1 week |