Please select the eligibility criteria that correspond to the clinical trial below.
Title: Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™
Brief Summary: Sepsis is a major cause of death in Intensive Care Units and therefore finding new therapies to improve survival rates and limit morbidity is a major goal. Over the past decades, blood purification has been proposed as an adjuvant therapy for sepsis. The goal of blood purification is to restore the immune homeostasis and efficiency through the removal of bacterial products including endotoxins, broad-spectrum cytokines and other inflammatory mediators. Indeed, the large and overwhelmed release of these mediators in the early phase of sepsis may induce multiple organ failure syndrome. In 2017, different techniques are proposed for blood purification. Among them, the highly adsorptive membrane, oXiris™, seems promising. This membrane can be used in case of Acute Kidney Injury associated with sepsis and exhibits enhanced blood purification capacities. Previous studies on animals have already proven that this membrane can remove broad-spectrum cytokines but also endotoxins from the blood. This ability to remove endotoxins is particularly interesting since endotoxins are believed to be the trigger of the immune cascade at the initiation of sepsis.

The lack of clinical evidence is the main limit to a wider use of this membrane. Therefore, the aim of the present clinical trial is to characterize the blood purification properties of the membrane in a human clinical setting. The oXiris™ membrane is specifically designed to improve the adsorptive capacities of the polyacrylonitrile-based AN69 membrane. Its extremely rich coating of polyethyleneimine (PEI) gives the membrane the ability to bind and remove not only cytokines but also endotoxins due to the positive charges of PEI at the surface of the membrane. The tested hypothesis is that the oXiris™ filter allows for a greater endotoxin and cytokine removal compared to a standard polysulfone ("PrismafleX HF1400") filter in patients with septic shock.


Options:
A: Inclusion Criteria:

* Male or female aged ≥ 18 years old,
* "Early" septic shock (in the first 12 hours after Intensive Care Unit (ICU) admission or readmission in the ICU after surgery), with lactatemia \> 2 mmol/L and norepinephrine needs \> 0.2 µg/kg/min 2 hours after the end of the initial surgery (to ensure that a potential anesthesia effect as disappeared),
* Secondary to a community-acquired or a nosocomial peritonitis (secondary or tertiary but not primary peritonitis),
* AKI KDIGO ≥ stage 2 or another indication for renal replacement therapy, according to the clinician in charge (if baseline creatinine is unknown, KDIGO ≥ stage 2 can be defined by a serum creatinine ≥ 2-fold the normal creatinine for age, gender, and ethnicity).

Exclusion Criteria:

* Inability to obtain informed consent from the patient or next of kin,
* Actual participation in another interventional study,
* Contraindications to citrate,
* Allergy to heparin,
* Pregnant or breastfeeding woman,
* Neutropenia \< 0.5 G/L resulting from chemotherapy or other iatrogenic causes
* Patient receiving immunosuppressive therapy, long-term corticosteroids, therapeutic antibodies, chemotherapy in the last 6 months (whatever the dose),
* Patient with innate or acquired immune deficiency (for example severe combined immunodeficiency, HIV or AIDS)
* Onco-hematological disease (lymphoma, leukemia, myeloma) treated within the last 5 years (but inclusion of a patient with solid cancer who did not receive chemotherapy during the past 6 months is possible),
* Patient with expected ICU length of stay \< 48 hours,
* Patient for whom a limitation of active care was pronounced at the time of enrollment,
* Patient with no social security insurance, with restricted liberty, or under legal protection.
B: Inclusion Criteria:

* Patients admitted on the Intensive Care Unit (ICU) requiring continuous venovenous hemofiltration.
* No high bleeding risk. A high bleeding risk is defined as a platelet count below 40 x 10\^9/L or APTT of more than 60 seconds or a PT-INR of more than 2.0 or a recent major bleeding or significant active bleeding i.e. requirement for more than two units of packed red blood cells as a transfusion within 24 hours of initiation of CVVH.

Exclusion Criteria:

* Less than 18 or over 80 years of age.
* Patients administered heparin or coumarins for other reasons will also be excluded.
* Patients with a HIT in known history will also be excluded.
C: Inclusion Criteria:

* Male or female critically ill patients over the age of 18 years old
* Acute Kidney Injury requiring CRRT defined using the Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification with criterion I or worse.
* Septic shock as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.
* Written informed consent obtained from the patient or a patient's legal representative
* Patient patient's legal representative able to agree to patient's enrollment in the study with informed consent.

Exclusion Criteria:

* Pregnancy
* Participation in another research study protocol
* Known heparin induced thrombopenia or contraindication to heparin
* Pre-existing chronic renal failure on chronic dialysis
* Therapeutic anticoagulation with heparin for another reason (e.g. chonic arrhythmia)
* Severe liver failure (15% prothrombin time)
D: Inclusion Criteria:

1. Patient must be receiving medical care in an intensive care unit (ICU) (e.g., medical ICU, surgical ICU, cardiothoracic ICU, Trauma ICU, Mixed ICU, other).
2. Adult patients with AKI or other serious conditions who require treatment with CRRT.
3. Patients are expected to remain in the ICU and on CRRT for at least 72 hours after randomization.
4. Patients already receiving standard-of-care CRRT must be randomized within 24 hours of initiation of their standard-of-care CRRT.

Exclusion Criteria:

1. Patients requiring systemic anticoagulation with antithrombotic agents for reasons other than CRRT. The exception is patients receiving subcutaneous heparin for deep vein thrombosis prophylaxis according to institutional practice or patients on aspirin may be enrolled.
2. Patients in whom citrate anticoagulation is contraindicated such as patients with a known allergy to citrate or who have experienced adverse events associated with citrate products including patients with a prior history of citrate toxicity or patients with uncorrected severe hypocalcemia (whether in the context of current citrate administration or due to the underlying disease state).
3. Patients who are not candidates for CRRT.
4. Patients who are receiving extracorporeal membrane oxygenation (ECMO) therapy.
5. Patients with severe coagulopathy \[i.e., platelets \< 30,000/mm3, international normalized ratio (INR) \> 2, partial thromboplastin time (PTT) \> 50 seconds\] including severe thrombocytopenia (platelets \< 30,000/mm3), HIT (heparin induced thrombocytopenia), ITP (idiopathic thrombocytopenia purpura), and TTP (thrombotic thrombocytopenia purpura) should not be enrolled in the trial.
6. Patients with fulminant acute liver failure or acute on chronic liver failure as documented by a Child-Pugh Liver Failure Score \> 10.
7. Patients with refractory shock associated persistent, worsening with lactic acidosis (lactate \> 4 mmol/L). However, patients with improving subsequent serum lactate levels may be enrolled.
8. Patients unlikely to survive at least 72 hours.
9. Female patients who are pregnant, lactating, or planning to become pregnant during the study period.
10. Patients who are currently participating in another interventional clinical study.
11. Patients with a medical condition that may interfere with the study objectives.

Answer: A