Please select the eligibility criteria that correspond to the clinical trial below.
Title: Regional Citrate Versus Systemic Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury
Brief Summary: The aim of this study is to evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality.


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:

1. Signed Written Informed Consent
2. 18 years of age or older
3. Ongoing treatment with any chronic dialysis treatment OR an estimated glomerular filtration rate (eGFR)\* \<20 ml/min/1.73 m2 at least twice 3 months apart of which at least one occasion is \<15 ml/min/1.73 m2 due to CKD during the last year (12 months).
4. Diagnosis of chronic (i.e., repeated) paroxysmal, persistent, or permanent atrial fibrillation (AF) or atrial flutter (AFL)
5. CHA2DS2-VASc score ≥2 or more for men ≥3 or more for women as an indication for oral anticoagulation
6. Women of childbearing potential (WOCBP) should have a negative highly effective pregnancy test at screening and must agree to follow instructions for method(s) of contraception for the duration of treatment

Exclusion Criteria:

Participants may not be included in the study if any of the following criteria are met:

1. AF or AFL due to reversible causes (e.g., thyrotoxicosis, pericarditis)
2. Any degree of rheumatic mitral stenosis or moderate-to-severe non-rheumatic mitral stenosis at the time of inclusion into the study
3. Any condition other than AF or AFL that requires chronic anticoagulation (e.g., a prosthetic mechanical heart valve, antiphospholipid syndrome).
4. Any contraindication for anticoagulation including

   1. endocarditis
   2. documented intolerance for apixaban
   3. liver disease with documented coagulation disorder
   4. pregnancy or breast feeding
5. Active bleeding or serious bleeding within 3 months, or

   1. documented hemorrhagic blood dyscrasia
   2. patients currently receiving dual antiplatelet therapy
6. Planned for surgery

   1. kidney transplantation with a living donor within 3 months
   2. active on the kidney transplant waiting list at a kidney transplant center where apixaban use is prohibited
   3. valvular heart disease surgery
7. Current use of strong inhibitors of both CYP3A4 and P-glycoprotein in accordance with the summary of product characteristics (SmPC) of apixaban or regular intake of non-steroidal anti-inflammatory drugs (NSAID) or cyclooxygenase-2 (COX2) inhibitors
8. Any condition or circumstance in which the patient should not participate in the study according to the study investigator (reason documented in the pre-screening protocol)

Being active on the kidney transplant waiting list is not an exclusion criterion if it is allowed according to the current clinical guidelines at the transplant clinic where the patient is registered. The patient must report changes in waiting list status to the investigator promptly.
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:

* age\>=18 years
* intermittent hemodialysis patients that carry on a 4 hours hemodialysis procedure, 2-3 times one week.
* the therapy mode is hemodialysis，with a dialysis fluid more than 500ml/min and blood flow volume more than 3.5-4ml/min.kg；
* at risk of hemorrhage,including active hemorrhage(within 3 days),post-operation(within 3 days) and pre-invasive operation(within 7 days).

Exclusion Criteria:

* at high risk of citrate accumulation( total bilirubin \>60umol/L; lactic acid\>3mmol/L,）；
* use the drugs that impact the coagulation function within 7 days;
* serious hypocalcemia (serum calcium\<1.9mmol/L).

Answer: A