Please select the eligibility criteria that correspond to the clinical trial below.
Title: Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke
Brief Summary: SYNTHESIS is a pragmatic multicenter randomized controlled trial (RCT), open-label, with blinded follow-up aiming to determine whether loco-regional intra-arterial (IA) with recombinant tissue-plasminogen activator (rt-PA) and/or mechanical devices, as compared with systemic intravenous (I.V.) infusion of rt-PA within 3 hours of ischemic stroke, increases the proportion of independent survivors at 3 months.


Options:
A: Inclusion Criteria

1. Age 18 and older
2. Clinical diagnosis of ischemic stroke and an associated score on the NIHSS of 5 or more points
3. Planned to undergo (or has undergone) intra-arterial (IA) thrombectomy and/or thrombolysis for acute hemispheric stroke. (Either as primary therapy or as adjuvant therapy following intravenous tPA treatment)
4. Planned to undergo or has undergone an MR brain scan including MR perfusion imaging (ASL \& bolus PWI) and MR angiography of the circle of Willis prior to IA therapy
5. Intra-arterial thrombectomy can be started within 90 minutes of completion of the MR perfusion scan and within 24 hours of symptom onset (Start of IA therapy is defined as the time of insertion of the femoral artery sheath; Time of brain scan is defined as the time that the scan is completed)
6. Able to obtain informed consent

Exclusion Criteria

1. Any pre-existing illness resulting in a modified Rankin Scale Score of 2 or higher prior to the qualifying stroke
2. Creatinine clearance \< 40 ml/min based on the NIDDK four-variable MDRD method (non-weight based)
3. Documented allergy to MR contrast agent
4. MRI contraindications (pacemaker, etc.)
5. Pregnancy
B: Inclusion Criteria:

* Sudden focal neurological deficit attributable to a stroke
* Clearly defined time of onset, allowing initiation of intravenous treatment within 3 hours of symptoms onset and intra-arterial treatment within 6 hour of symptoms onset.
* Age greater than 18 years

Exclusion Criteria:

* Disability preceding stroke consistent with a modified Rankin scale score of 2-4
* Coma at onset
* Rapidly improving neurological deficit
* Seizure at onset
* Clinical presentation suggestive of a subarachnoid hemorrhage
* Previous history of intracranial hemorrhage
* Septic embolism
* Arterial puncture at a non compressible site within the previous 7 days
* Any traumatic brain injury within the previous 14 days
* Surgery of the central nervous system in the previous 3 months
* Gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 14 days.
* Current therapy with intravenous or subcutaneous heparin to rise the clotting time
* Known hereditary or acquired hemorrhagic diathesis, baseline INR greater than 1.5, aPTT more than 1.5 times normal, or baseline platelet count less than 100,000 per cubic millimeter
* Baseline blood glucose concentrations below 2.75 mm/L (50 mg/dL).
* Known contrast sensitivity.
* Women of childbearing potential (unless pregnancy impossible) or known to be breastfeeding. Uncontrolled hypertension defined by a blood pressure greater or equal 185 mmHg systolic or diastolic greater or equal 110 mm Hg in 3 separate occasions at least 10 minutes apart or requiring continuous IV therapy.
* Prognosis very poor regardless of therapy; likely to be dead within months.
* Unlikely to be available for follow-up (eg, no fixed home address, visitor from overseas).
* Any other condition which local investigators feels would pose a significant hazard in terms of risk/benefit to the patient, or if therapies are impracticable.

COMPUTED TOMOGRAPHIC (CT) SCAN EXCLUSION CRITERIA

* Intracranial tumors except small meningioma
* Hemorrhage of any degree
* Acute infarction (since this may be an indicator that the time of onset is uncorrected)
C: Inclusion Criteria:

1. Age ≥18 years;
2. Acute ischemic stroke consistent with infarction in the basilar artery territory;
3. Basilar artery occlusion confirmed by CTA/MRA/DSA, within 8 hours of estimated occlusion time;
4. Written informed consent from patient or surrogate, if unable to provide consent.

Exclusion Criteria:

1. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of Cerebral hemorrhage on presentation;
2. Premorbid mRS ≥ 3 points;
3. Currently in pregnant or lactating;
4. Known serious sensitivity to radiographic contrast agents and nitinol metal;
5. Current participation in another investigation drug or device study;
6. Uncontrolled hypertension defined as systolic blood pressure \> 185 mmHg or diastolic blood pressure \> 110 mmHg that cannot be controlled except with continuous parenteral antihypertensive medication;
7. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with INR \>1.7 or institutionally equivalent prothrombin time;
8. Baseline lab values: glucose \< 50 mg/dl or \> 400 mg/dl, platelets \<100\*109/L, or Hct\<25%;
9. Arterial tortuosity that would prevent the device from reaching the target vessel;
10. Life expectancy less than 1 year;
11. History of major hemorrhage in the past 6 months;
12. Angiographic evidence of significant cerebellar mass effect or acute hydrocephalus.
13. Angiographic evidence of bilateral extended brainstem ischemia.
D: 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)

Answer: B