Clopidogrel for Acute Ischaemia of Recent Onset (CAIRO)

Clopidogrel Loading for Acute Ischaemia of Recent Onset (CAIRO)

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Cerebrovascular Accident
• Intervention / Treatment: Drug: Clopidogrel; Drug: Aspirin

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11566
    • Ain Shams University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 900 mg Clopidogrel; 67 patients will receive 12 tablets clopidogrel ( each 75 mg) as total 900 mg each patient	Drug: Clopidogrel; there is 2 groups one group will receive 900 mg Clopidogrel and the other will receive 600 mg Clopidogrel; Other Names: Srtoka
ACTIVE_COMPARATOR: 600 mg Clopidogrel; 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; there is 2 groups one group will receive 900 mg Clopidogrel and the other will receive 600 mg Clopidogrel; Other Names: Srtoka
PLACEBO_COMPARATOR: 400 mg Aspirin; 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; there's another group will receive 400 mg Aspirin; Other Names: Aspocid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Ramez R Moustafa, MD PhD MRCP, Department of Neurology, Ain Shams University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): February 1, 2019
• Study Completion (ACTUAL): February 1, 2019

Study Registration Dates

• First Submitted: May 2, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (ESTIMATE): May 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 10, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: CAIRORCT