Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparing Cytokines, Toxins Adsorbing oXiris Filter to ST150 Filter During CRRT in Patients With Septic Shock
Brief Summary: The Oxiris® filter is a registered product for CRRT already safely used in routine care.

In in vitro experiments, the Oxiris® filter has been demonstrated to adsorb endotoxin and cytokines. Compared to conventional filters this may be advantageous in patients with severe sepsis but neither decreased levels of endotoxin and cytokines nor an improved outcome has been demonstrated with clinical use.

But there are so far little clinical data on the oXiris® filter on humans. The oXiris® filter will be investigated in a double blind randomized crossover setting against a traditional filter (ST150). Either filter will be used for 24 hours after which it will be changed to the opposite filter for another 24 hours.

Arterial blood samples will be drawn at start and then 1, 3, 8, 16 and 24 hours after the start of each filter, and analyzed for endotoxin (EAA assay), TNF-α, IL-1β, IL-6 and IL-10 (ELISA) levels. Standard blood tests will be analyzed simultaneously. Data concerning mode and settings of CRRT, heart rate, blood pressure, medication, data concerning ventilatory support and pathogen will be registered.

Primary endpoint: Levels of endotoxin and cytokines will be compared using Student's paired t-test on AUC values for each 24-hour period.


Options:
A: Inclusion Criteria:

1. Patients admitted to intensive care unit (ICU) of age \>18 years with decision based on the clinical situation of the patient taken by the physician in charge that continuous renal replacement therapy will be started.
2. Vasoconstrictor and volume dependent septic shock with known Gram-negative infectious agent in blood culture.
3. Vasoconstrictor and volume dependent septic shock suspected to be caused by a Gram-negative agent and with positive plasma endotoxin test.

Exclusion Criteria:

1. Infected with Hepatitis B or C or HIV.
2. Dependence on dialysis treatment before the actual ICU episode.
B: Inclusion Criteria:

* Age 18 or older and able to sign consent (or surrogate).
* Must have been referred to the inpatient Nephrology consult service for evaluation of acute kidney injury (AKI).
* Expected survival of at least 48 hours.

Exclusion Criteria:

* Hemoglobin \< 8 g/dl
* Serum potassium ≥6.5 milliequivalents per liter (mEq/L)
* Weight \> 120kg.
C: Inclusion Criteria:

1. Injury stage of RIFLE criteria or more: \> 2-fold increase in the serum creatinine or urine output \< 0.5 mL/kg/hr for 12 hours
2. Patients with any dialysis treatment before admission to the ICU or patients with end-stage renal failure and receiving dialysis
3. Informed consent has been obtained.

Exclusion Criteria:

1. patient age \< 20 years or \> 85 years
2. life expectancy less than 3 months (ex. terminal stage of malignancy)
3. Child-Pugh class C liver cirrhosis
4. pregnancy or lactation
5. history of anticoagulation prior to the randomization
6. bleeding tendency (platelet count \< 50,000/ul, INR \> 2.5, PTT \> 65, or fibrinogen \< 1.00 g/L)
7. history of hemorrhagic disease (ex. GI bleeding, cerebral hemorrhage, pulmonary hemorrhage)
D: 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

Answer: A