Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Safety Study Assessing Oral Anticoagulation With Apixaban Versus Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD) on Chronic Hemodialysis Treatment
Brief Summary: The Study is an open-labeled, randomized controlled trial, phase IIIb. Its objective is to assess the safety of the factor Xa inhibitor apixaban versus the vitamin-K antagonist (VKA) phenprocoumon in patients with NVAF and ESKD on hemodialysis. The safety will be assessed by means of the incidence of major and clinically relevant, non-major bleeding on anticoagulation.


Options:
A: 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
B: Inclusion Criteria:

* chronic stable HD patients ≥ 18 years
* on HD at least three times per week for at least 3 months

Exclusion Criteria:

* contraindication to heparin
* currently using heparin-free HD
* known clotting disorder
* on warfarin therapy
* dialyzing with a dysfunctional central venous catheter (blood flow rates consistently less than 300mL/min and/or frequent use of thrombolytic)
* history of vascular access dysfunction
* planned vascular access conversion or procedure during the study period
* use of high calcium dialysate
* active medical issue requiring hospitalization
* planned kidney transplant during the study period
* planned conversion of dialysis modality (peritoneal dialysis, nocturnal dialysis) during the study period
* unable to provide informed consent
C: Inclusion Criteria:

* willingness to give written informed consent for participation in the study
* age 18-80 years old
* ability to understand and follow instructions and able to participate in the study for the entire period
* clinically stable (based on the investigator's judgment) within the three months prior to the screening visit
* written and signed agreement

Exclusion Criteria:

* antecedents of cerebrovascular accident, documented myocardial infarction, coronary angioplasty or bypass surgery within 6 months prior to the screening visit
* currently enrollment in any other investigational device or drug study, or participation in another clinical study within 30 days prior to the screening visit
* known or suspected drug or alcohol abuse
* known congenital or acquired bleeding disorders including hepatic failure and amyloidosis, present active major bleeding;
* increased risk of hemorrhage, due to: pericarditis or bacterial endocarditis, severe uncontrolled hypertension, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, shortly after brain, spinal or ophthalmological surgery, concomitant treatment with platelet inhibitors, recent surgical procedures (especially with hemorrhagic complications or those in which hemorrhagic complications would be very severe - cardio-vascular, ophthalmological or neurological), planned surgical procedure within the next week, (history of) heparin-induced thrombocytopenia, with any other disease which, in the opinion of the investigator, makes unacceptable his/her inclusion in the study (known hypersensitivity to heparin, benzyl alcohol, or pork products that should not be treated with innohep®, severe psychiatric disorders, age \<18 years, malignant disorders and a life expectancy \<6 months, patients that were involved in another research study (studies) in the last month.
D: 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.

Answer: D