Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-Blind, Placebo-Controlled, International, Multicentre, Phase III Study to Investigate the Efficacy and Safety of Ticagrelor and ASA Compared With ASA in the Prevention of Stroke and Death in Patients With Acute Ischaemic Stroke or Transient Ischaemic Attack
Brief Summary: Study to investigate if the study drug ticagrelor and ASA is more effective than Placebo (inactive tablet) and ASA in preventing new stroke events


Options:
A: Inclusion Criteria:

* Men or women equal or elder 40 years of age
* Either acute ischaemic stroke or high-risk TIA as defined here and randomisation occurring within 24 hours after onset of symptoms

Key Exclusion Criteria:

* Planned use of antithrombotic therapy in addition to study medication including antiplatelets (eg, open label ASA, GPIIb/IIIa inhibitors, clopidogrel, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol) and anticoagulants (eg, warfarin, oral thrombin and factor Xa inhibitors, bivalirudin, hirudin, argatroban, unfractionated and low molecular weight heparins). - Any history of atrial fibrillation, ventricular aneurysm or suspicion of cardioembolic pathology for TIA or stroke. - Planned carotid, cerebrovascular, or coronary revascularisation that requires halting study medication within 7 days of randomisation. - Receipt of any intravenous or intra-arterial thrombolysis or mechanical thrombectomy within 24 hours prior to randomisation - History of previous symptomatic non-traumatic intracerebral bleed at any time (asymptomatic microbleeds do not qualify), gastrointestinal (GI) bleed within the past 6 months, or major surgery within 30 days.
B: Inclusion criteria:

* Adult subjects (male or female≥40 years)
* Acute non-disabling ischemic stroke (NIHSS≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
* TIA (Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with study drug within 24 hours of symptoms onset and with moderate-to-high risk of stroke recurrence (ABCD2 score≥4 at the time of randomization).Symptom onset is defined by the "last see normal" principle
* Informed consent signed

Exclusion Criteria:

* Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI
* Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI
* Modified Rankin Scale Score\>2 at randomization (pre-morbid historical assessment)
* NIH Stroke Score≥4 at randomization
* Clear indication for anticoagulation(presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis)
* Contraindication to clopidogrel or ASA
* Known allergy
* Severe renal or hepatic insufficiency
* Severe cardiac failure, asthma
* Hemostatic disorder or systemic bleeding
* History of hemostatic disorder or systemic bleeding
* History of thrombocytopenia or neutropenia
* History of drug-induced hematologic or hepatic abnormalities
* Low white blood cell (\<2 x109/l) or platelet count (\<100 x109/l)
* Use of thrombolysis within 24 hours prior to randomization
* History of intracranial hemorrhage
* Anticipated requirement for long-term non-study antiplatelet drugs, or NSAIDs affecting platelet function
* Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation
* Gastrointestinal bleed or major surgery within 3 months
* Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months (if clinically indicated, vascular imaging should be performed prior to randomization whenever possible)
* Scheduled for surgery or interventional treatment requiring study drug cessation
* Qualifying TIA or minor stroke induced by angiography or surgery
* Severe non-cardiovascular comorbidity with life expectancy \< 3 months
* Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test
* Currently receiving an investigational drug or device
C: Inclusion Criteria:

1. Provision of signed informed consent prior to any study-specific procedure
2. ≥40 years of age
3. Acute onset of cerebral ischaemia due to

   1. AIS with NIHSS ≤5. AIS is defined as acute onset of neurological deficit attributed to focal brain ischaemia, and either of the following:

      * Persistent signs or symptoms of the ischaemic event at the time o randomisation, OR
      * Acute ischaemic brain lesion documented before randomisation by computed tomography (CT) scan or magnetic resonance imaging (MRI) (diffusion-weighted imaging) and that could account for the clinical presentation
   2. High-risk TIA, defined as neurological deficit of acute onset attributed to focal ischaemia of the brain by history or examination with complete resolution of the deficit, and at least one of the following:

      * ABCD2 score ≥6 and TIA symptoms not limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo
      * Symptomatic intracranial arterial occlusive disease that could account for the clinical presentation, documented by transcranial Doppler or vascular imaging and defined as at least 50% narrowing in the diameter of the vessel lumen
      * Internal carotid arterial occlusive disease that could account for the clinical presentation, documented by Doppler, ultrasound, or vascular imaging and defined as at least 50% narrowing in diameter of the vessel lumen
4. Randomisation occurring within 24 hours after onset of symptoms; for wake-up strokes (when the time of symptom onset is not known), within 24 hours from the time point at which the patient was reported to be in their normal condition
5. CT or MRI performed after symptom onset ruling out intracranial haemorrhage or other pathology, such as vascular malformation, tumour, or abscess that according

to the Investigator could explain symptoms or contraindicate study treatment

Exclusion Criteria:

1. Need for or an anticipated need for any of the following:

   1. Dual antiplatelet therapy with ASA and P2Y12 inhibitors (including patients with carotid artery stenting and percutaneous coronary intervention)
   2. Antiplatelets other than ASA (eg, GPIIb/IIIa inhibitors, clopidogrel, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol, ticagrelor) and other antithrombotic agents with antiplatelet effects, including traditional/herbal medicine agents
   3. Anticoagulants (eg, warfarin, oral thrombin and factor Xa inhibitors, bivalirudin, hirudin, argatroban, fondaparinux, or unfractionated heparin and long-term treatment with low-molecular weight heparins). Short-term treatment (≤7 days) with low-dose low-molecular weight heparin may be used in immobilised patients at the discretion of the Investigator
2. Any history of atrial fibrillation/flutter, ventricular aneurysm, or suspicion of other cardioembolic pathology for TIA or stroke
3. Patients who should receive or have received any intravenous or intra-arterial thrombolysis or mechanical thrombectomy within 24 hours prior to randomisation
4. Planned carotid endarterectomy that requires halting investigational product within 3 days of randomisation or is expected to require unblinding of investigational product (planned carotid endarterectomy is in itself not an exclusion criterion)
5. History of previous intracranial haemorrhage at any time (asymptomatic microbleeds do not qualify), gastrointestinal haemorrhage within the past 6 months, or major surgery within 30 days
6. Patients considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second- or third-degree atrioventricular block) unless already treated with a permanent pacemaker
7. Inability of the patient to understand and/or comply with study procedures and/or follow-up, in the opinion of the Investigator
8. Known hypersensitivity to ticagrelor or ASA
9. Need for or an anticipated need for oral or intravenous therapy with any of the following:

   1. Strong cytochrome P450 3A (CYP3A4) inhibitors (eg, ketoconazole, clarithromycin \[but not erythromycin or azithromycin\], nefazadone, ritonavir, atazanavir) that cannot be stopped for the course of the study
   2. Long-term (\>7 days) non-steroidal anti-inflammatory drugs
10. Known bleeding diathesis or coagulation disorder (eg, thrombotic thrombocytopenic purpura)
11. Known severe liver disease (eg, ascites or signs of coagulopathy)
12. Renal failure requiring dialysis
13. Pregnancy or breastfeeding. Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator
14. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
15. Previous enrolment or randomisation in the present study
16. Participation in another clinical study with an investigational product at any time during the 30 days prior to randomisation (regardless of when treatment with the investigational product was discontinued)
D: Inclusion Criteria:

* Neurological deficit (based on history or exam) attributed to focal brain ischemia and EITHER:

  * High risk TIA: Complete resolution of the deficit at the time of randomization AND ABCD2 score of (greater than or equal to) 4 OR
  * Minor ischemic stroke: residual deficit with NIHSS of (less than or equal to) 3 at the time of randomization
* Ability to randomize within 12 hours of time last known free of new ischemic symptoms.
* Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
* Ability to tolerate aspirin at a does of 50-325 mg/day.

Exclusion Criteria

* Age \<18 years
* TIA symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo.
* In the judgment of the treating physician, a candidate for thrombolysis, endarterectomy or endovascular intervention, unless the subject declines both endarterectomy and endovascular intervention at the time of evaluation for eligibility.
* Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event.
* Gastrointestinal bleed or major surgery within 3 months prior to index event.
* History of nontraumatic intracranial hemorrhage.
* Clear indication for anticoagulation (e.g., warfarin, heparin) anticipated during the study period (atrial fibrillation, mechanical heart valve, deep venous thrombosis, pulmonary embolism, antiphospholipid antibody syndrome, hypercoagulable state).
* Qualifying ischemic event induced by angiography or surgery.
* Severe non-cardiovascular comorbidity with life expectancy \<3 months.
* Contraindication to clopidogrel or aspirin.

  * Known allergy
  * Severe renal (serum creatinine \>2 mg/dL or 176.8umol/L) or hepatic insufficiency (prior or concurrent diagnosis, with International Normalized Ratio (INR)\>1.5 or any resultant complication, such as variceal bleeding, encephalopathy, or icterus)
  * Hemostatic disorder or systemic bleeding in the past 3 months
  * Current thrombocytopenia (platelet count \<100 x10\^9/l) or neutropenia (\<1 x10\^9/l)
  * History of drug-induced hematologic or hepatic abnormalities
* Anticipated requirement for long-term (\>7 day) non-study antiplatelet drugs (eg, dipyridamole, clopidogrel, ticlopidine), or Non-steroidal Anti-inflammatory Drugs (NSAIDs) affecting platelet function (such as prior vascular stent or arthritis).
* Inability to swallow medications.
* At risk for pregnancy: premenopausal or post menopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence).
* Unavailability for follow-up.
* Signed and dated informed consent not obtained from patient.
* Other neurological conditions that would complicate assessment of outcomes during follow-up.
* Ongoing treatment in another study of an investigational therapy that may potentially interact with study drug, or treatment in such a study within the last 7 days.
* Previously enrolled in the POINT study.

Answer: C