Please select the eligibility criteria that correspond to the clinical trial below.
Title: RENal Hemodialysis Patients ALlocated Apixaban Versus Warfarin in Atrial Fibrillation (RENAL-AF) Randomized Clinical Trial
Brief Summary: This is a prospective, randomized, open-label, blinded end-point evaluation trial. The patient population consists of patients on hemodialysis who have atrial fibrillation (AF) and end-stage renal disease (ESRD) .


Options:
A: Inclusion Criteria:

1. Critically ill patients with clinical indication for CRRT (clinical decision to use continuous RRT due to hemodynamic instability)

   Or

   Severe acute kidney injury (KDIGO 3-classification) despite optimal resuscitation
2. At least one of the following conditions

   * Sepsis or septic shock
   * Use of catecholamines (norepinephrine or epinephrine ≥ 0.1 µg/kg/min or norepinephrine ≥ 0.05 µg/kg/min + dobutamine (any dose) or norepinephrine ≥ 0.05 µg/kg/min + vasopressin (any dose) or epinephrine ≥ 0.05 µg/kg/min + norepinephrine ≥ 0.05 µg/kg/min)
   * Refractory fluid overload: worsening pulmonary edema: PaO2/FiO2 \< 300 mmHg and/or fluid balance \> 10% of body weight)
3. 18-90 years old
4. Intention to provide full intensive care treatment for at least 3 days
5. Written informed consent of the patient or the legal representatives or the authorized representative or the inclusion due to an emergency situation

Exclusion Criteria:

1. Patients with increased bleeding risk (e.g. an active bleeding from ulcers in the gastro-intestinal tract, hypertension with a diastolic blood pressure higher than 105 mm Hg, injuries (intracranial hemorrhage, aneurysm of brain arteries) of or surgical procedures on the central nervous system if a heparinization with a target aPTT 45-60 s is not allowed by the treating neurologist or neurosurgeon, severe retinopathies, bleeding into the vitreum, ophthalmic surgical procedures)) or injuries, active tuberculosis; infective endocarditis)
2. Disease or organ damage related with hemorrhagic diathesis (coagulopathy, thrombocytopenia, severe liver or pancreas disease)
3. Dialysis-dependent chronic kidney insufficiency
4. Need of therapeutic systemic anticoagulation
5. Allergic reaction to one of the anticoagulants or ingredients, Heparin-induced thrombocytopenia
6. AKI caused by permanent occlusion or surgical lesion of the renal artery
7. AKI caused by (glomerulo)nephritis, interstitial nephritis, vasculitis or postrenal obstruction
8. Do-not-resuscitate order
9. Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura
10. Persistent and severe lactate acidosis in the context of an acute liver failure and/or shock
11. Kidney transplant within the last 12 months
12. Pregnancy and nursing period
13. Abortus imminens
14. No hemofiltration machine free for use at the moment of inclusion
15. Participation in another clinical intervention trial in the last 3 months
16. Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
17. Persons held in an institution by legal or official order
B: Inclusion Criteria:

* end stage renal failure treated with chronic hemodialysis
* atrial fibrillation
* CHA2DS2-VASc Score ≥ 2
* ability to provide informed consent

Exclusion Criteria:

* known intestinal malabsorption or inability to take oral medication
* inability to stop co-medication that causes major interactions with rivaroxaban (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, ritonavir, rifampicin, phenytoin, carbamazepine, phenobarbital or St John's wort)
* investigator's assessment that the subject's life expectancy is less than 1 year
* prosthetic mechanical heart valve
* contraindication for anticoagulation
* liver dysfunction Child-Pugh grade B-C
* pregnancy, breastfeeding, inadequate contraception
* incompliance with medication and scheduled investigations
C: Inclusion Criteria:

* End-stage kidney disease (ESKD) with chronic hemodialysis treatment 3 times per week (with about at least 3.5 hours per dialysis)
* Chronic (i.e. repeated) paroxysmal, persistent or permanent atrial fibrillation (AF) or atrial flutter (AFL) documented by standard or Holter ECG on at least 2 separate days before (or apart from) hemodialysis procedures
* Increased risk of stroke or systemic embolism identified by a CHA2DS2-VASc score of 2 or more as an indication for oral anticoagulation
* Patients with ischemic stroke that meet the above criteria, can be included after more than 3 months if not severely handicapped (modified Rankin scale 0 or 1 of 6, i.e. no symptoms or no significant disability and able to carry out all usual activities, despite some symptoms (Farrell, Godwin, Richards, and Warlow (1991))
* Males and females, aged 18 or older

Exclusion Criteria:

* AF or AFL due to reversible causes (e.g., thyrotoxicosis, pericarditis)
* Patients with a new onset of hemodialysis within the last 3 months
* Clinically significant (moderate or severe) aortic and mitral stenosis
* Conditions other than AF or AFL that require chronic anticoagulation (e.g., a prosthetic mechanical heart valve).
* Active infective endocarditis
* Any planned interventional or surgical AF or AFL ablation procedure
* Any active bleeding
* A serious bleeding event in the previous 6 months before screening
* Inadequately controlled (HbA1c levels \>8.5%) or untreated diabetes
* History of malignant neoplasms at high risk of current bleeding (see summary of product characteristics (SmPC) of study drugs)
* Known indication for treatment with NSAIDs (see SmPC of study drugs) - acetylsalicylic acid (ASA) up to 100 mg per day is allowed
* Known Antiphospholipid Syndrome requiring anticoagulation
* Impaired liver function e.g., caused by active infection with HIV, HBV or HCV, hepatitis or other liver damage (No limits for ALT and AST values are defined in this study protocol, although mentioned in the SmPC because they are frequently elevated in dialysis patients. In case of clinically relevant increase of ALT or AST level, patient's eligibility is to be decided by the responsible investigator)
* Any type of stroke within 3 months prior to baseline
* Other indication for anticoagulation than AF or AFL
* Valvular heart disease requiring surgery
* A high risk of bleeding (e.g., active peptic ulcer disease, a platelet count of \<100,000 per cubic millimeter or hemoglobin level of \<8 g per deciliter)
* Documented hemorrhagic tendencies or blood dyscrasias
* Current alcohol or drug abuse
* Life expectancy of less than 1 year
* Indication for dual platelet inhibition at baseline (ASA ≤ 100 mg/day is allowed, clopidrogel is excluded at any dose).
* Active infection or symptoms suggestive of COVID-19 infection.
D: Inclusion Criteria:

* Males and females, age at least 18 years, or the local age of consent, whichever is greater.
* Patients with AF defined as AF on ECG at enrollment or two or more reports of AF from separate monitoring events at least 2 weeks apart (report of ECG, Holter monitor, event monitor or implantable loop recorder).
* CHA2DS2-VASc score of ≥ 2.
* End-stage renal disease treated with hemodialysis for ≥ 3 months.
* Considered by the treating physician(s) to be candidate for oral anticoagulation.
* If of childbearing potential, be willing to avoid pregnancy during the study.

Exclusion Criteria:

* Not considered by the treating physician(s) to be candidates for oral anticoagulation (for example, hemoglobin \< 8.5g/dL, history of intracranial hemorrhage, active bleeding, recent gastrointestinal bleed or retroperitoneal bleed, severe hepatic impairment, or anaphylactic reaction to apixaban)
* Moderate or severe mitral stenosis
* Conditions other than AF that require anticoagulation such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism
* Need for aspirin at a dose \> 81 mg a day or need for P2Y12 antagonist therapy (for example clopidogrel, prasugrel, or ticagrelor)
* Life expectancy \< 3 months
* Anticipated kidney transplant within the next 3 months
* Prisoners or others who are involuntarily incarcerated or detained
* Pregnant, breastfeeding, or considering pregnancy.
* Participation in a clinical trial of an experimental treatment within the past 30 days

Answer: D