Please select the eligibility criteria that correspond to the clinical trial below.
Title: JASAP: Japanese Aggrenox Stroke Prevention vs. Aspirin Programme, Phase III Study to Compare the Preventive Effect of Recurrent Brain Infarction and Safety of Aggrenox (Combination Drug Containing Sustained-release Dipyridamole 200 mg/Acetylsalicylic Acid 25 mg) Twice Daily vs. Acetylsalicylic Acid 81 mg Once Daily
Brief Summary: Phase III study to compare the preventive effect of recurrent brain infarction and safety of Aggrenox (combination drug containing sustained-release dipyridamole 200 mg/acetylsalicylic acid 25 mg) twice daily vs. acetylsalicylic acid 81 mg once daily


Options:
A: Inclusion Criteria:

Patients with a diagnosis of cerebral infarction (excluding cardiogenic cerebral embolism) who meet the diagnostic criteria based on the National Institute of Neurological Disorders and Stroke (NINDS) ad hoc committee's classification of cerebrovascular disease III.

1. Patients who have had an onset of cerebral infarction, the time of which is known, between 1 week and 6 months before the time of enrolment (including first and recurrent cerebral infarctions)
2. Patients who are 50 years or older
3. Patients whose neurological signs and symptoms are considered to be stable by the investigator or sub-investigator
4. Patients with a finding corresponding to the responsible focus confirmed by head X-ray computerised tomography (CT) or magnetic resonance imaging (MRI)
5. Patients who have at least two of the following risk factors:

   * diabetes
   * hypertension (systolic blood pressure is 140 mmHg or higher or diastolic blood pressure is 90 mmHg or higher) or under treatment of hypertension
   * smoker (at the time of onset of cerebral infarction)
   * obesity (Body mass index (BMI) is more than 25 kg/m2)
   * previous vascular disease (stroke, acute myocardial infarction or peripheral arterial disease before the onset of cerebral infarction)
   * end-organ damage (retinopathy, left ventricular hypertrophy (LVH) or microalbuminuria)
   * hyperlipidaemia

Exclusion Criteria:

1. Patients with a diagnosis of brain disorders with a bleeding risk such as brain haemorrhage, subarachnoid haemorrhage, cerebral arteriovenous (AV) malformation, cerebral AV aneurysms and brain tumours
2. Patients with complications of cardiac disorders (atrial fibrillation, mitral valve stenosis, severe cardiac valve disorders) that may provide an embolic source for cerebral embolism
3. Patients having had acute coronary syndromes (acute myocardial infarction, unstable angina) within 6 months after enrolment in this study
4. Patient with hypersensitivity to dipyridamole preparations
5. Patients with a history of drug allergy to acetylsalicylic acid (ASA) or aspirin asthma
6. Patients with a history of peptic ulcer
7. Patients having undergone arterial reconstruction after development of cerebral infarction
8. Patients with very severe impairment (4 or 5 on Modified Rankin Scale)
9. Patients with bleeding or bleeding tendencies (haemophilia, haemorrhage urinary tract, vitreous haemorrhage, etc.)
10. Patients with severe hypertension (systolic blood pressure is 180 mmHg or higher or diastolic blood pressure is 110 mmHg or higher)
11. Patients with complications such as serious cardiac, renal and hepatic disorders
12. Patients with a malignant tumour or having had a tumour treatment in the past 5 years
13. Women who are or may be pregnant or lactating women
B: INCLUSION:

Small subcortical ischemic stroke or subcortical TIA.

Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met:

* One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting \> 24 hrs within the past 6 months
* Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc.
* No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric.
* No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician.
* Subcortical TIA with corresponding lesion on DWI.
* MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(\<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote).

EXCLUSION:

To be eligible for entry into the study, the patient must not meet any of the criteria listed below:

* Disabling stroke (Modified Rankin Scale less than or equal to 4)
* Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
* Age under 30 years
* High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc)
* Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets
* Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA
* Prior ipsilateral carotid endarterectomy
* Impaired renal function: GFR \<40
* Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR)
* A score \< 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination
* Medical contraindication to MRI
* Pregnancy or women of child-bearing potential who are not following an effective method of contraception
* Geographic or social factors making study participation impractical
* Unable or unwilling to provide informed consent
* Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits
* Patients concurrently participating in another study with an investigational drug or device
* Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)
C: Inclusion Criteria:

* Patients with TIA or minor acute ischemic stroke (NIHSS \< 4 at the time of randomization) who must NOT be candidates for acute thrombolysis or other acute intervention indicated as the current standard of care
* Aged 40 years or older
* Patients with: (a) weakness at time of TIA/minor stroke and/or language disturbance at time of TIA/minor stroke and; (b) duration of neurological deficit (TIA) \> 5 minutes
* Patients can be randomized within 24 hours of symptom onset. Symptom onset is defined by the "last seen well" principle
* Patients must have provided written, informed consent to participate in the FASTER trial.

Exclusion Criteria:

* Patients with pure sensory symptoms, pure vertigo or dizziness, pure ataxia or pure visual loss
* Patients for whom thrombolysis or other acute intervention is indicated as the current standard of care
* Patients who are currently on statin therapy, antiplatelet therapy (not including aspirin), or long-term non-steroidal anti-inflammatory drugs (NSAIDs but not COX inhibitors), or anticoagulation
* Patients who in the opinion of the site Investigator, should be commenced on statin therapy
* Patients with neurological deficit due to intracranial hemorrhage (intracranial hemorrhage, subarachnoid hemorrhage, subdural hematoma, epidural hematoma), tumor, infection or any finding not consistent with acute brain ischemia as the cause of presenting symptoms
* Presumed cardiac source of embolus (e.g. atrial fibrillation, prosthetic cardiac valve, known/suspected endocarditis)
* Patient with a concomitant acute coronary syndrome (acute myocardial infarction or unstable angina)
* Modified Rankin Score 3 or more (pre-morbid historical assessment)
* Patients in whom the qualifying event was due to a complication of cerebral angiography, a revascularization procedure or trauma
* Uncontrolled hypertension at baseline (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg), or malignant hypertension defined by brain plus acute organ involvement due to acute hypertension
* Women who are breast-feeding or pregnant. Women of childbearing potential must have a negative pregnancy test prior to randomization. Women of childbearing potential may still participate in the trial but must plan on not becoming pregnant during the course of the study and must practice a suitable method of birth control. If a patient becomes pregnant or begins breast-feeding during the study, both study drugs will be discontinued immediately, and the patient followed for the duration of the study
* Evidence of contraindication for use of Trial Medication: (i) serious systemic bleeding precluding antiplatelet therapy; (ii) hypersensitivity to aspirin, thienopyridine drugs (clopidogrel or ticlopidine) or statins; (iii) current or past history of renal insufficiency \[serum Creatinine \>150 umol\]; (iv) hepatic dysfunction indicated by any or all of the following \[ALT \>3xULN, AST \>3xULN, ALP \>3xULN\]; (v) thrombocytopenia \[platelet count \< 150 x10\^9/L\]; (vi) neutropenia \[neutrophil count \< 0.5 x10\^9/L\]; (vii) bleeding diathesis or coagulopathy indicated by any or all of the following \[INR \>1.2, PT \>1.2xULN, PTT \>1.2xULN\]
* Life expectancy of less than 90 days
* Participation in another clinical therapeutic trial (drug or device) either concurrently or within the previous 30 days, or prior participation in FASTER
* Geographical or other factors that render follow-up impractical or that render evaluation of outcome events impossible (e.g. severe dementia). Patients may be randomized who could and are willing to complete their follow-up at a participating centre
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: A