Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of Edoxaban (DU-176b) Versus Warfarin In Subjects With Atrial Fibrillation - Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE - AF TIMI - 48)
Brief Summary: This study is to demonstrate the safety and efficacy profile, in two different dose regimens of Edoxaban (DU-176b), (an investigational new drug being tested for the prevention of stroke/systemic embolic events (SEE)), in individuals with atrial fibrillation. Patients will be randomized to one of three treatment groups: High Dose Regimen, Low Dose Regimen, \& Warfarin. The expected duration of the study is 24 months.


Options:
A: Inclusion Criteria:

* 21 years of age or older; male or female.
* Able to provide written informed consent.
* History of documented AF within the prior 12 months
* A moderate to high risk of stroke, as defined by CHADS2 index score of at least 2

Exclusion Criteria:

* Transient atrial fibrillation secondary to other reversible disorders
* Subjects with moderate or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve
* Subjects with any contraindication for anticoagulant agents;
* Subjects with conditions associated with high risk of bleeding or have known or suspected hereditary or acquired bleeding disorders
* Females of childbearing potential including the following:

  * Females with a history of tubal-ligation
  * Females less than 2 years post-menopausal
B: Inclusion Criteria:

* Males and females ≥ 18 yrs with atrial fibrillation (AF) and one or more of the following risk factors for stroke:
* Age ≥ 75, previous stroke
* transient ischemic attack (TIA) or Systemic Embolism (SE)
* Symptomatic congestive heart failure or left ventricular dysfunction with left ventricular ejection fraction (LVEF) ≤ 40%
* Diabetes mellitus or hypertension requiring pharmacological treatment
C: Inclusion criteria Patients with non-valvular atrial fibrillation (AF), at moderate to high risk of stroke, or systemic embolism with at least one additional risk factor (i.e. previous ischemic stroke, TIA, or systemic embolism, left ventricular dysfunction, age \>=75 years, age \>=65 with either diabetes mellitus, history of coronary artery disease or hypertension)

Exclusion criteria

1. Prosthetic heart valves requiring anticoagulation per se, or hemodynamically relevant valve disease that is expected to require surgical intervention during the course of the study
2. Severe, disabling stroke within the previous 6 months, or any stroke within the previous 14 days
3. Conditions associated with an increased risk of bleeding
4. Contraindication to warfarin treatment
5. Reversible causes of atrial fibrillation (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism).
6. Plan to perform a pulmonary vein ablation or surgery for cure of the AF
7. Severe renal impairment (estimated creatinine clearance \<=30 mL/min)
8. Active infective endocarditis
9. Active liver disease
10. Women who are pregnant, lactating, or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study
11. Anaemia (haemoglobin \<100g/L) or thrombocytopenia (platelet count \<100 x 109/L)
12. Patients who have developed transaminase elevations upon exposure to ximelagatran
13. Patients who have received an investigational drug in the past 30 days or are participating in another drug study
14. Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, has a life expectancy less than the expected duration of the trial due to concomitant disease, or has any condition which in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse)
15. Any known hypersensitivity to galactose if the warfarin used contains galactose.
D: Inclusion Criteria:

* Written informed consent according to country specific details
* Age: ≥18 years
* Acute ischemic stroke, either confirmed by MRI or CT scan (tissue based definition) or by sudden focal neurological deficit of presumed ischaemic origin that persisted beyond 24 hours and otherwise normal non-contrast CT scan. Please note: prior intravenous or endovascular treatment is allowed.
* Permanent, persistent, or paroxysmal spontaneous AF previously known or diagnosed during the index hospitalization
* Agreement of treating physician to prescribe DOACs

Exclusion Criteria:

* Atrial fibrillation due to reversible causes (e.g. thyrotoxicosis, pericarditis, recent surgery, myocardial infarct)
* Valvular disease requiring surgery
* Mechanical heart valve(s)
* Moderate or severe mitral stenosis. Please note that other valvular diseases and biological valves are eligible
* AF and conditions other than AF that require anticoagulation, including therapeutical dose of low-molecular-weight heparin or heparin. Please note: infratherapeutic anticoagulation at ischaemic stroke onset defined as follows is not an exclusion criteria:

  * Vitamine K antagonist: International Normalized Ratio (INR) \<1.7
  * Anti-IIa: thrombin time \<80 seconds and/or anti-IIa \<50 ng/ml
  * Anti-Xa: anti-Xa \<50 ng/ml
* Subject who is contraindicated to DOACs
* Female who is pregnant or lactating or has a positive pregnancy test at time of admission
* Patients with serious bleeding in the last 6 months or is at high risk of bleeding (e.g. active peptic ulcer disease, platelet count \< 100'000/mm3 or haemoglobin \< 10 g/dl or INR ≥ 1.7, documented haemorrhagic tendencies or blood dyscrasias)
* Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day)
* Severe comorbid condition with life expectancy \< 6 months
* Severe or moderate renal insufficiency as defined by creatinine clearance \< 50 ml/min
* Subject who requires haemodialysis or peritoneal dialysis
* Subject with aortic dissection
* Current participation in another investigational trial
* Dual antiplatelet therapy at baseline or strong likelihood to be treated with dual antiplatelet therapy during the course of the trial
* CT or MRI evidence of haemorrhage classified as PH1 (defined as parenchymal haemorrhage = blood clots in \<30% of the infarcted area without or with slight space-occupying effect) and PH2 (defined as blood clots in \>30% of the infarcted area with a substantial space-occupying effect) independently of clinical deterioration. Please note that HI1 (defined as haemorrhagic infarct = small petechiae along the margins of the infarct) and HI2 (defined as confluent petechiae within the infarcted area but no space occupying effect) are acceptable if not associated with clinical deterioration and if the treating physician feels comfortable to treat patients with DOACs.
* CT or MRI evidence of mass effect or intra-cranial tumour (except small meningioma)
* CT or MRI evidence of cerebral vasculitis
* Endocarditis
* Evidence of severe cerebral amyloid angiopathy if MRI scan performed

Answer: A