Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study of DU-176b in Patients With NVAF Aged 80 Years or Older Who Are Ineligible for Available Oral Anticoagulation Therapy
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of edoxaban in patients with non-valvular NVAF aged 80 years or older who are ineligible for available oral anticoagulation therapy.


Options:
A: 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.
B: Inclusion Criteria:

1. Aged 18 years or over
2. Clinical diagnosis of acute ischaemic stroke
3. AF, confirmed by any of:

   1. 12-lead ECG recording
   2. Inpatient ECG telemetry
   3. Other prolonged ECG monitoring technique (e.g. Holter monitor)
   4. Known diagnosis of atrial fibrillation verified by medical records (e.g. primary care records, letter from secondary care)
4. Eligibility to commence DOAC in accordance with approved prescribing recommendations confirmed by treating physician
5. Uncertainty on the part of the treating physician regarding early versus standard initiation of DOAC.

Exclusion Criteria:

1. Contraindication to anticoagulation:

   1. Coagulopathy or current or recent anticoagulation with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomisation.
   2. Thrombocytopenia (platelets \< 75 x 10⁹/L)
   3. Other coagulopathy or bleeding tendency (based on clinical history or laboratory parameters) judged to contraindicate anticoagulation by treating clinician
2. Contraindication to early anticoagulation

   1. Known presence of haemorrhagic transformation with parenchymal haematoma occupying \>30% of the infarct volume and exerting significant mass effect (i.e. PH2) (NB: HI1, HI2 and PH1 are not considered contraindications)
   2. Presence of clinically significant intracranial haemorrhage unrelated to qualifying infarct
   3. Any other contraindication to early anticoagulation as judged by the treating clinician
3. Contraindication to use of DOAC:

   1. Known allergy or intolerance to both Factor Xa inhibitor and direct thrombin inhibitor
   2. Definite indication for VKA treatment e.g. mechanical heart valve, valvular AF, antiphospholipid syndrome
   3. Severe renal impairment with creatinine clearance (Cockcroft \& Gault formula) \<15 mL/min (i.e. 14 mL/min or less)
   4. Liver function tests ALT \> 2x ULN
   5. Cirrhotic patients with Child Pugh score equating to grade B or C
   6. Patient is taking medication with significant interaction with DOAC, including:

      * Azole antifungals (e.g. ketoconazole, itraconazole)
      * HIV protease inhibitors (e.g. ritonavir)
      * Strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)
      * Dronedarone
4. Pregnant or breastfeeding women
5. Presence on acute brain imaging of non-stroke pathology judged likely to explain clinical presentation (e.g. mass lesion, encephalitis)
6. Inability for patient to be followed up within 90 days of trial entry
7. Patient or representative refusal to consent to study procedures, including the site informing GP and healthcare professional responsible for anticoagulation care of participants
8. Any other reason that the PI considers would make the patient unsuitable to enter OPTIMAS.

Note that current DOAC treatment is NOT an exclusion criterion, as long as the treating physician considers it appropriate to restart (or continue) according to the timings specified in the OPTIMAS trial protocol. Continuation of the DOAC would be recorded as a start time of zero hours.
C: Inclusion Criteria:

* Patients with Nonvalvular Atrial Fibrillation (NVAF) aged 80 years or older who are ineligible for available oral anticoagulation therapy

Exclusion Criteria:

* Patients with active bleeding
* Patients who have poorly controlled hypertension
* Patients who have liver dysfunction accompanied with disorder of blood coagulation
D: Inclusion Criteria: All of below

* Acute ischemic stroke or TIA presumed to be cardioembolic origin (within 5 days from stroke onset) with mild severity: infarct size on DWI less than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
* Atrial fibrillation including paroxysmal atrial fibrillation: atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary).
* Age ≥19 years
* Informed consent

Exclusion Criteria: Any of below

* Chronic renal failure (GFR less than 30ml/min) or severe hepatic impairment
* Significant hemorrhagic transformation (parenchymal hematoma type I or II by the ECASS definition)
* Stroke mechanism of presumed small vessel occlusion: single small subcortical infarct in the perforating artery territory
* Large hemispheric or cerebellar infarction; larger than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
* Mechanical valve requiring warfarin therapy
* Active internal bleeding
* Prior history of symptomatic intracranial bleeding

  : patients with asymptomatic bleedings or microbleedings on MRI are eligible for inclusion
* Major surgery or major trauma within 30 days that might be associated with increased bleeding risk
* Clinically significant gastrointestinal bleeding within 6 months
* Intravenous tissue plasminogen activator use or mechanical embolectomy within 48 hours plus 'significant hemorrhagic transformation as described above (exclusion criteria 2)' or 'large hemispheric infarction or cerebellar infarction as described above (exclusion criteria 4)'

  : patients achieving successful reperfusion without hemorrhage nor large infarction are eligible for enrollment
* Severe anemia: hemoglobin \<10 g/dL
* Bleeding diathesis; thrombocytopenia (\<90,000/µL, prolonged PT (INR\>1.7)
* Sustained uncontrolled hypertension: SBP \>180 mmHg or DBP \>100 mmHg
* Severe devastating illness, such terminal cancer, hepatic failure; therefore, the participants have a life expectancy less than 6 months.
* Planned invasive procedure with potential for uncontrolled bleeding, including major surgery

Answer: C