Please select the eligibility criteria that correspond to the clinical trial below.
Title: EARLY: Prospective, Randomised, National, Multi-centre, Open-label, Blinded Endpoint Study to Compare Aggrenox b.i.d. (200 mg Dipyridamole MR + 25 mg Acetylsalicylic Acid) When Started Within 24 Hours of Stroke Onset on an Acute Stroke Unit, and Aggrenox b.i.d. When Started After a 7-day Therapy With ASA 100 mg Once Daily Outside Off an Acute Stroke Unit, in Symptomatic Ischaemic Stroke Patients Over a Three Months Treatment Period an Exploratory Study
Brief Summary: German stroke units are hesitating to use Aggrenox for secondary ischaemic stroke / transient ischaemic attack (TIA) prevention in a sub-acute treatment setting. They argue that clinical experience with sub-acute Aggrenox treatment is limited and poorly documented when compared with sub-acute acetylsalicylic acid (ASA) treatment. However, long term treatment (started after 3-6 months after stroke/TIA) with Aggrenox was safe and superior to ASA treatment in preventing recurrent strokes. There is no evidence for ASA to prevent from neurological progression after stroke during the first 3 months. Results from a cohort study suggest that starting Aggrenox within 72 hours after stroke predicts clinical improvement in the National Institute of Health Stroke Scale (NIHSS) at discharge from the hospital. Dipyridamole suppresses acute inflammatory responses to stroke.

This study is designed to investigate the tolerability and efficacy of a secondary stroke prevention treatment with Aggrenox when initiated within 24 hours of stroke onset on a stroke unit compared to later initiation after a 7 day ASA treatment and outside off a stroke unit setting.


Options:
A: 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)
B: Inclusion Criteria:

* Patients who receive explanation on this study and give informed consent
* Patients aged 30 to 85 years
* Baseline NIHSS less than 15
* Onset of symptoms within 48 hours of the start of investigational product
* Full functional independence prior to the present stroke indicated by an mRS score of 0, 1, 2

Exclusion Criteria:

* Evidence from CT or MRI scan of an acute intracranial hemorrhage, a tumor, encephalitis or any diagnosis other than acute ischemic stroke likely to cause the present symptoms.
* Previous regular use of an antiplatelet agent or warfarin
* Patients with known cardiac disease likely to cause cardiogenic embolism or congestive heart failure
* Evidence from CT or MRI scan of midline shift when visiting hospital
* Uncontrolled hypertension (SBP\>220 mmHg or DBP\>120 mmHg)
* Hypotension (\<90/60 mmHg)
* Patients with known bleeding diathesis or coagulation disorder
* Patients with liver disease (ALT\>100 or AST\>100), or renal disease (creatinine\>2.0 mg/dl)
* Known severe anaemia (hemoglobin\<8.0 mg/dl), or thrombocytopenia (platelet\<100,000/mm3)
* Scheduled for endarterectomy within 3 months
* Severe co-morbidity likely to limit patient's life expectancy to less than 6 months
* Patients with alcohol or illegal drug abuse or dependency
* Pregnant or lactating patients. When administrating to females, it should be confirmed that the patients is in the menopause (by evaluation of investigators) or permanently infertile (hysterectomy or surgical operation like bilateral tubal ligation, bilateral oophorectomy, etc). If a patient is likely to be pregnant, the patient should not be pregnant before randomization. And, the patient should use reliable contraception between at least 3 weeks before randomization to 7 days after the final administration of study drug.
* Patients treated by thrombolytic agents like tPA after onset of stroke
C: 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
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