Please select the eligibility criteria that correspond to the clinical trial below.
Title: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
Brief Summary: A transient ischemic attack (TIA) is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. An ischemic stroke is a cerebral infarction. In POINT, eligibility is limited to brain TIAs and to minor ischemic strokes (with an NIH Stroke Scale \[NIHSS\] score less than or equal to 3).

TIAs are common \[25\], and are often harbingers of disabling strokes. Approximately 250,000-350,000 TIAs are diagnosed each year in the US. Given median survival of more than 8 years \[32\], there are approximately 2.4 million TIA survivors. In a national survey, one in fifteen of those over 65 years old reported a history of TIA \[33\], which is equivalent to a prevalence of 2.3 million in older Americans. Based on the prevalence of undiagnosed transient neurological events, the true incidence of TIA may be twice as high as the rates of diagnosis \[33\]. Based on our review of the National Inpatient Sample for 1997-2003, there were an average of 200,000 hospital admissions for TIA each year, with annual charges climbing quickly in the period to $2.6 billion in 2003.

Composite endpoint of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death at 90 days.


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:

* Adults (≥ 18 years)
* The participant is able to give informed consent.
* Established atherothrombotic cardiovascular disease (CVD) or high cardiovascular risk, of for individuals without established cardiovascular disease, a calculated 5 year CVD risk of 15% or greater (calculated using the 1991 Anderson Framingham risk equation with adjustments as defined by the New Zealand Guidelines Group recommendations)
* The trial Investigator considers that each of the polypill components are indicated
* The trial Investigator is unsure as to whether a polypill-based strategy or usual care is better.

Exclusion Criteria:

* Contraindication to any of the components of the polypill (e.g. known intolerance to aspirin, statins, or ACE inhibitors,pregnancy or likely to become pregnant during the treatment period).
* The treating doctor considers that changing a participant's cardiovascular medications would put the participant at risk (e.g. symptomatic heart failure, high dose βblocker required to manage angina or for rate control in atrial fibrillation,accelerated hypertension, severe renal insufficiency, a history of severe resistant hypertension)
* Known situation where medication regimen might be altered for a significant length of time, e.g. current acute cardiovascular event, planned coronary bypass graft operation.
* Unlikely to complete the trial (e.g. lifethreatening condition other than cardiovascular disease) or adhere to the trial procedures or attend study visits (e.g. major psychiatric condition, dementia).
C: Inclusion criteria:

* Ischemic stroke with a brain lesion visualized by neuroimaging (either brain Computed Tomography (CT) or Magnetic Resonance Image (MRI)). The visualized stroke is a non-lacunar infarct , e.g. involving the cortex or \>1.5 cm (\>2.0 cm if measured on MRI diffusion-weighted images) in largest diameter if exclusively subcortical.Visualization by CT usually requires delayed imaging \>24-48 hours after stroke onset.
* The index stroke must have occurred either up to 3 months before randomization (Modified Rankin Scale(mRS) \<=3 at randomization) or up to 6 months before randomization (mRS \<=3 at randomization) in selected patients that are \>= 60 years plus at least one additional risk factor for recurrent stroke.
* Arterial imaging or cervical plus Transcranial Doppler (TCD) ultrasonography does not show extra-cranial or intracranial atherosclerosis with \>= 50% luminal stenosis in artery supplying the area of acute ischemia.
* As evidenced by cardiac monitoring for \>= 20 hours with automated rhythm detection, there is absence of AF \> 6 minutes in duration (within a 20 hour period, either as single episode or cumulative time of multiple episodes).

Further inclusion criteria apply.

Exclusion criteria:

* Modified Rankin Scale of \>=4 at time of randomization or inability to swallow medications.
* Major risk cardioembolic source of embolism such as: a) intracardiac thrombus as evidenced by transthoracic or transesophageal echocardiography, b) paroxysmal, persistent or permanent Atrial fibrillation (AF), c) atrial flutter, d) prosthetic cardiac valve (mitral or aortic, bioprosthetic or mechanical), e) atrial myxoma, f) other cardiac tumors, g) moderate or severe mitral stenosis, h) recent (\< 4weeks) myocardial infarction, i) valvular vegetations, or j) infective endocarditis.
* Any indication that requires treatment with an anticoagulant as per Investigator's judgment.
* History of atrial fibrillation (unless it was due to reversible causes such as hyperthyroidism or binge drinking, and has been permanently resolved).
* Other specific stroke etiology (i.e. cerebral arteritis or arterial dissection, migraine with aura/vasospasm, drug abuse).
* Renal impairment with estimated creatinine clearance (as calculated by Cockcroft-Gault equation) \<30mL/min at screening, or where Investigator expects creatinine clearance is likely to drop below 30mL/min during the course of the study.

Further exclusion criteria apply.
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: D