Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIIB, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS)
Brief Summary: PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy and safety of intravenous (IV) alteplase in participants with mild acute ischemic strokes that do not appear to be clearly disabling. Participants will be randomized in a 1:1 ratio to receive within 3 hours of last known well time either 1) one dose of IV alteplase and one dose of oral aspirin placebo or 2) one dose of IV alteplase placebo and one dose of oral aspirin 325 milligrams (mg).


Options:
A: Inclusion Criteria:

* Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of less than or equal to(\</=) 5 and determined as not clearly disabling by the investigator
* Study treatment initiated within 3 hours of last time participant seen normal

Exclusion Criteria:

* Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following:

  1. CT with clear large hypodensity that is greater than (\>) one-third middle cerebral artery (MCA) territory (or \>100 cubic centimeter \[cc\] if not in MCA territory)
  2. MRI with clear large hyperintensity on concurrent diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) that is greater than one-third MCA territory (or greater than 100 cc if not in MCA territory),
  3. Imaging lesion consistent with acute hemorrhage, or
  4. Evidence of intraparenchymal tumor
* Disability prior to the presenting stroke
* Standard contraindications to IV alteplase within 3 hours of symptom onset, including:

  1. Head trauma, myocardial infarction, or previous stroke within the previous 3 months
  2. Gastrointestinal or urinary tract hemorrhage within the previous 21 days
  3. Major surgery within the previous 14 days
  4. Arterial puncture at non-compressible site within the previous 7 days
  5. Any history of ICH with the exception of those less than (\<) 5 chronic microbleeds on MRI
  6. Elevated blood pressure defined by systolic blood pressure \>185 millimeters of mercury (mm Hg) or diastolic blood pressure \>110 mm Hg, or treatments requiring aggressive measures to achieve acceptable levels
  7. Treatment with unfractioned heparin within past 48 hours and activated partial thromboplastin time outside normal range
  8. Blood glucose \<50 milligrams per deciliter (mg/dL)
  9. International normalized ratio \>1.7
  10. Platelet count \<100,000 per cubic millimeter (/mm\^3)
  11. Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban) within the last 48 hours
* Allergic reaction to study drug, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs)
* Females of childbearing age who are known to be pregnant and/or lactating
* Inability to swallow, which would prevent oral intake of aspirin or aspirin placebo tablet
* Other serious, advanced, or terminal illness that would confound the clinical outcome at 90 days
* Current or recent (within 3 months) participation in another investigational drug treatment protocol
* Anticipated inability to obtain 3-month follow-up assessments
* Previous enrollment in PRISMS
* Any other condition deemed by the investigator that would pose hazard to the participant with alteplase treatment
B: 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)
C: Inclusion Criteria:

* Diagnosis of ischemic stroke with an onset within 72 hours prior to start of study agent administration, male or female.
* Supratentorial ischemic stroke involving the cortex documented by neurological exam and confirmed by MRI.
* Stroke involving upper extremity.
* Subjects who received thrombolytic therapy may be enrolled and the use of antiplatelet is acceptable.

Exclusion Criteria:

* Any other severe acute or chronic medical or psychiatric condition besides the stroke.
* Women of child bearing potential.
* Uncontrolled hypertension.
D: Inclusion Criteria:

-Clinical diagnosis of ischaemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Symptoms must be distinguishable from an episode of generalised ischaemia (i.e. syncope), seizure, or migraine disorder.

Main inclusion criteria:

* Patients at risk of stroke who have had transient ischaemia of the brain or completed ischaemic stroke due to thrombosis
* Symptoms of ischaemic attack began less than 24 hours prior to study medication start, are to be present for at least 30 minutes and have not significantly improved before start of treatment
* Patients are eligible for platelet inhibiting treatment
* National Institute of Health Stroke Scale (NIHSS) between 5 and 20 (at pre-screening and screening)
* Actual Modified Rankin Scale (mRS) (at baseline) is worse than retrospective mRS (before stroke)
* A contraindication for stroke lysis is given
* Patients are able to give (at least oral) informed consent and to swallow either medication

Exclusion Criteria:

* Hypersensitivity to any of the components of the product or salicylates.
* Patients with active gastric or duodenal ulcers or with bleeding disorders.
* Pregnancy during the third trimester.
* Lysis therapy.
* A platelet inhibiting therapy with Acetylsalicylic Acid (ASA) doses of more than 100 mg per day, or with clopidogrel of any dose has been planned or started.
* Time of onset of stroke symptoms is unknown (when a stroke happened during night-/sleeping time, bedtime is assumed as time of onset)

Answer: A